Koji Tamura

Impact of the angiotensin II receptor antagonist, losartan, on myocardial fibrosis in patients with end-stage renal disease: assessment by ultrasonic integrated backscatter and biochemical markers.

Myocardial fibrosis commonly occurs in patients with end-stage renal disease (ESRD) and has proven to be an important predictor for cardiovascular events. In experimental settings, angiotensin II type 1 receptor (AT1-R) antagonists have been shown to have anti-fibrotic effects on the myocardium independent of their antihypertensive effects. In this study, to investigate whether the AT1-R antagonist losartan would have such anti-fibrotic effects in patients, we administered losartan or, for purpose of comparison, the angiotensin-converting enzyme enalapril or Ca2+-antagonist amlodipine to patients with ESRD. Thirty-nine ESRD patients with hypertension were randomly assigned to receive losartan (n=13), enalapril (n=13), or amlodipine (n=13). Ultrasonic integrated backscatter (IBS) and serological markers of collagen type I synthesis and degradation were used to assess the degree of myocardial fibrosis just before and after 6 months of treatment. There were no significant differences in antihypertensive effects among the three agents. In the enalapril- and amlodipine-treated groups, the mean calibrated IBS values increased significantly after 6 months of treatment (enalapril: −31.6±1.3 to −29.4±1.2 dB, p=0.011; amlodipine: −30.6±1.4 to −27.2±1.2 dB, p=0.012). However, the mean calibrated IBS values in the losartan-treated group did not increase after 6 months of treatment (−31.2±1.7 to −31.3±1.4 dB, p=0.88). The ratio of the serum concentration of procollagen type I carboxy-terminal peptide to the serum concentration of collagen type I pyridinoline cross-linked carboxy-terminal telopeptide was significantly reduced in the losartan-treated group (42.6±4.6 to 34.4±3.6, p=0.038). The present study indicates that losartan more effectively suppresses myocardial fibrosis in patients with ESRD than does enalapril or amlodipine despite a comparable antihypertensive effect among the three drugs.

Association of preceding angina with in-hospital life-threatening ventricular tachyarrhythmias and late potentials in patients with a first acute myocardial infarction

We studied 140 patients with a first acute myocardial infarction to examine the effect of preceding angina as a marker of ischemic preconditioning on clinical ventricular arrhythmias and late potentials. Preceding angina was defined as the presence of ischemic chest pain within 24 hours before onset of myocardial infarction lasting no longer than 30 minutes and seen three or more times per day or at rest. Clinical features, angiographic findings, and late potentials were compared between patients with and without preceding angina. Thirty-four (24%) patients had preceding angina. Although the incidence of life-threatening ventricular tachyarrhythmias significantly differed (p = 0.0219), other clinical findings, including presence of late potentials, were not different between the two groups. Of 14 patients with life-threatening ventricular tachyarrhythmias, five events were considered as reperfusion arrhythmias. In patients who had successful reperfusion therapy, the incidence of life-threatening ventricular tachyarrhythmias had a tendency to be lower in patients with preceding angina than in those without preceding angina (p = 0.0586). Severe angina within 24 hours of onset of acute myocardial infarction is suggested to reduce occurrence of life-threatening ventricular tachyarrhythmias mainly associated with reperfusion during hospitalization.

Prognostic impact of plasma brain natriuretic peptide for cardiac events in elderly patients with congestive heart failure.

Background: Plasma brain natriuretic peptide (BNP) has been reported to be useful in determining the prognosis of patients with ischemic heart disease and cardiomyopathy. However, aging increases the level of plasma BNP; therefore, the prognostic impact of plasma BNP in elderly patients with congestive heart failure has not been fully established. Objective: We sought to determine whether plasma BNP could predict recurrent cardiac events in elderly patients with congestive heart failure. Methods: Forty-eight consecutive elderly patients (>65 years old) were enrolled in the present study. All patients were admitted with their first episode of congestive heart failure. Clinical characteristics, plasma BNP, left ventricular ejection fraction, and left ventricular mass index were compared between patients with and those without recurrent cardiac events. Results: During the follow-up period, twelve cardiac events were observed. The New York Heart Association functional class was signi- ficantly higher in patients with cardiac events than in those without (p < 0.05). The plasma BNP level in pa- tients with cardiac events was significantly higher than in those without (521.0 ± 156.0 vs. 126.8 ± 20.1 pg/ml, p < 0.001), despite more frequent treatment with angiotensin-converting enzyme inhibitors (75 vs. 28%, p < 0.05). The left ventricular ejection fraction was significantly lower and the left ventricular mass index higher in patients with cardiac events as compared with those without (38.1 ± 5.0 vs. 49.2 ± 2.4%, p < 0.05; 193.8 ± 14.3 vs. 132.6 ± 7.8 g/m2, p < 0.001, respectively). The plasma BNP was selected as an independent factor associated with cardiac events besides New York Heart Association functional class, left ventricular ejection fraction, and left ventricular mass index using multivariate Cox proportional-hazards regression analysis (hazard ratio = 2.656, p < 0.05). The cardiac event rate was significantly higher in patients with a plasma BNP concentration >132 pg/ml using Kaplan-Meier analysis (p < 0.001). Moreover, the plasma BNP level correlated inversely with the length of time from hospital discharge to a cardiac event (r = –0.575, p < 0.05). Conclusion: Measuring the plasma BNP level before hospital discharge in elderly patients with congestive heart failure was more useful than other conventional examinations for predicting the recurrence of cardiac events.

Determinants of ventricular arrhythmias in hemodialysis patients. Evaluation of the effect of arrhythmogenic substrate and autonomic imbalance.

Background/Aims: In chronic hemodialysis patients, we evaluated determinants of repetitive ventricular tachyarrhythmias which included late potentials and heart rate variability. Methods: We compared the presence of late potentials and heart rate variability obtained by ambulatory electrocardiogram (ECG), findings of echocardiography, and laboratory data between patients with and those without ventricular arrhythmias of Lown class 4A or 4B. Ambulatory ECG was recorded for 24 h from the beginning of hemodialysis. Heart rate variability was evaluated by the standard deviation of the normal RR interval (SDNN). Results: Thirty patients (17%) had ventricular arrhythmias of Lown class 4A or 4B. They were older than patients without such arrhythmias (p = 0.0021). Left-ventricular wall motion score (2.0 ± 3.9 and 0.3 ± 1.2, respectively, p < 0.0001) and left-ventricular mass index (167 ± 59 and 140 ± 44 g/m2, respectively, p = 0.0053) were larger in patients with ventricular arrhythmias of Lown class 4A or 4B than in those without. Stepwise logistic regression analysis was performed to select variables related to ventricular arrhythmias of Lown class 4A or 4B from the following 8 candidate variables; age, sex, presence of ischemic heart disease, diabetic nephropathy as the primary renal disease, presence of late potentials, SDNN, left-ventricular wall motion score and left-ventricular mass index. Higher left-ventricular wall motion score (p < 0.0001), older age (p = 0.0022) and male sex (p = 0.0235) were the variables associated with ventricular arrhythmias of Lown class 4A or 4B. Conclusion: In patients receiving hemodialysis, predominantly with chronic glomerulonephritis, ventricular arrhythmias of Lown class 4A or 4B were not associated with arrhythmogenic substrate revealed by late potentials or autonomic dysfunction assessed by heart rate variability. Left-ventricular wall motion abnormalities, age and sex were significant factors.

Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus

Abstract. The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55±11 vs 63±12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120±12 vs 145±16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1.81±0.29 vs 2.27±0.20, respectively, P<0.01). During the follow-up period (18± 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%±16.87% vs 12.89%±11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant statistical differences between the control group and non-survivors in terms of age (54±11 vs 73±11 years, respectively, P<0.01), H/M ratio (2.27± 0.20 vs 1.64±0.36, respectively, P<0.01) and %WR (12.89%±11.94% vs 42.52%±22.39%, respectively, P<0.01). In conclusion, cardiac sympathetic denervation using MIBG scintigraphy observed in hypertensive NIDDM patients, and was more profound in non-survivors. MIBG scintigraphy proved useful for the evaluation of NIDDM patients with new onset hypertension, and it was found that NIDDM patients with abnormalities on MIBG scintigraphy needed to be observe carefully.

Prevalence, resolution, and determinants of late potentials in patients with unstable angina and left ventricular wall motion abnormalities.

Although transient myocardial ischemia such as exercise-induced ischemia has not been reported to be associated with the occurrence of late potentials, the association of late potentials with more profound ischemic damage, which is represented by reversible but prolonged left ventricular wall motion abnormalities, has not been demonstrated. We prospectively evaluated 37 unstable angina patients who had reversible but prolonged wall motion abnormalities after resolution of chest pain and electrocardiogram (ECG) changes. Signal-averaged ECG (SAECG) and echocardiogram were recorded during the acute phase and before hospital discharge. Late potentials were present in 6 (16 percent) patients on the initial SAECG recording and resolved in all 6 patients on the second recording before hospital discharge. Normalization of inferior left ventricular wall motion abnormality and multivessel disease were observed more frequently in patients with late potentials on the initial recording than in patients without (p < 0.05 and p < 0.05, respectively). In conclusion, late potentials were observed in patients who had reversible but prolonged wall motion abnormalities; these late potentials were resolved with improvement of left ventricular wall motion abnormalities. These results suggest that myocardial ischemia with prolonged wall motion abnormalities is a possible mechanism of the occurrence of late potentials.

Long-term prognosis of medically treated patients with acute myocardial infarction and one-vessel coronary artery disease

Long-term prognosis was studied in 156 patients with acute myocardial infarction (AMI) with 1-vessel coronary artery disease (CAD). During a mean follow-up period of 110 months, 19 patients (14%) had reinfarction, 15 (9.6%) died (including 7 deaths of cardiac origin) and 15 (9.6%) were hospitalized for worsening of angina. A coronary arteriogram was obtained twice in 54 patients. The coronary arteriogram revealed multivessel CAD in all cases with reinfarction (n = 14). Ten percent of the patients with multivessel disease experienced a reinfarction during the initial 3 years after the onset of the first AMI. The recurrence rate of AMI in patients with 1-vessel disease increased gradually from the third year after the onset of their first AMI, reaching 10% in 6.7 years. The recurrence of AMI at the same region as the original infarction was detected in only 1 patient. Six of 19 patients (32%) with recurrence of AMI died and 13 survived after the reinfarction. It was difficult to predict future progression from the outcome of the comparison between the first and second coronary arteriograms. Thus, in patients with uncomplicated AMI with 1-vessel CAD, the prognosis is relatively good and the frequency of reinfarction is very low with conservative treatment.

I-123 MIBG cardiac imaging in diabetic neuropathy before and after epalrestat therapy.

I-123 metaiodobenzylguanidine (MIBG) scintigraphy is a new method to evaluate cardiac sympathetic nerve disturbance in patients with diabetes mellitus. Epalrestat specifically inhibits aldose reductase and improves diabetic neuropathy. The authors report a case of improvement in cardiac sympathetic dysfunction using MIBG scintigraphy with epalrestat therapy. In this case, epalrestat effectively reversed diabetic neuropathy, and MIBG scintigraphy was useful to evaluate the effect of epalrestat.

Late potentials during left ventricular healing of acute myocardial infarction.

BackgroundLate potentials and left ventricular remodeling are important factors in the prognosis of acute myocardial infarction. However, the relationship between late potentials and ventricular remodeling has not been fully evaluated. MethodsWe evaluated clinical characteristics, coronary angiographie findings and radionucltde angiographie measures about 1 month after an acute myocardial infarction in patients with and without late potentials. ResultsAlthough the left ventricular ejection fraction of patients with late potentials was not different from that of patients without late potentials, the left ventricular end-diastolic volume of patients with late potentials was larger than that of patients without late potentials (P<0.05). There was a significant positive correlation between the left ventricular end-diastolic volume and the filtered QRS duration (r = 0.53, P< 0.001). The root mean square of the voltage in the terminal 40ms and the low-amplitude signal duration of 7lt;40 μV in the terminal QRS sequence were also correlated with the left ventricular end-diastolic volume (r = 0.40, P<0.02, and r = 0.39, P<0.02, respectively). Patency of the infarct-related vessel in the late phase of an acute myocardial infarction was an important factor associated with the occurrence of late potentials (P<0.01). ConclusionA larger left ventricular end-diastolic volume in patients with late potentials might be associated with left ventricular remodeling during the first month after an acute myocardial infarction.

The effect of platelet-activating-factor antagonist TCV-309 on arrhythmias and functional recovery during myocardial reperfusion

BackgroundWe investigated the effects of a platelet-activating-factor antagonist TCV-309, an antagonist of metabolites of ischemia, on arrhythmias and functional recovery during in-situ reperfusion in dogs. MethodsOpen-chest anesthetized dogs were subjected to ligation of the left anterior coronary artery. Ischemia was maintained for 20 min after which reperfusion was allowed. A cardiac surface ECG was recorded continuously with the II limb lead. Monophasic action potential, left ventricular segment shortening measured by sonomicrometer, and left ventricular pressure were recorded simultaneously under atrial pacing (group A, n =14). In a second group of dogs, TCV-309 (1 mg/kg) was administered before coronary artery occlusion (group B, n = 12). The hearts were constantly paced through the right atrium at 120beats/min throughout all experiments. Measurements were continuously obtained from before drug administration to 30 min after reperfusion. ResultsThe 90% repolarization time of monophasic action potentials in group B revealed significant recovery compared with group A until the fifth minute after reperfusion (P<0.02). Reduction of severe ventricular arrhythmias was observed during reperfusion in group B (P<0.05). The percentage segment shortening and left ventricular pressure did not differ significantly between the groups. ConclusionThe platelet-activating-factor antagonist had beneficial effects on arrhythmias but not on functional recovery during reperfusion after brief coronary artery occlusion in situ in dogs.