Satoshi Tokunaga

Long-term Administration of Atrial Natriuretic Peptide in Patients with Acute Heart Failure

A short-term treatment of atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, is reported to improve cardiac performance in patients with chronic heart failure. However, clinical usefulness of long-term administration of ANP in patients with congestive heart failure has not been reported. We studied 36 patients with severe acute heart failure who resisted various therapy. Hemodynamic parameters were measured before and 48 h after initiating ANP infusion (n = 18) or normal saline (n = 18). Mean pulmonary capillary wedge pressure (23-->13 mm Hg), mean right atrial pressure (10-->5 mm Hg), systemic vascular resistance (2,169-->1,307 dyn x s x cm(-5)) and pulmonary vascular resistance (318-->136 dyn x s x cm(-5)) decreased significantly, whereas cardiac index (1.9-->2.6 L/min/m2) and urine volume (1,692-->2,560 ml/day) increased during long-term ANP infusion (before-->48 h). Moreover, in eight patients with long-term ANP infusion, these hemodynamic effects were maintained at 7 days after initiating ANP infusion. Vasodilating, pulmonary vasorelaxant, and diuretic activities of ANP are maintained without tolerance, and thus long-term ANP infusion is clinically useful in patients with severe acute heart failure.

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.

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.

Heart rate variability and left ventricular dilatation early after myocardial infarction.

To assess clinically whether alterations of autonomic tone precede left ventricular dilatation, heart rate variability and early left ventricular dilatation after a first myocardial infarction were assessed. Low-frequency power (LF), high-frequency power (HF), and total power (TP) were obtained by ambulatory electrocardiogram on day 1 in 53 patients with a first acute myocardial infarction. Left ventricular end-diastolic volume determined by echocardiography was obtained on day 1 and day 14. Stepwise linear regression analysis was used to assess the associations of early left ventricular dilatation with heart rate variability adjusted for clinical variables. Higher LF and TP were significantly associated with early left ventricular dilatation after adjustment for age, sex, site of myocardial infarction, acute revasucularization, peak creatine kinase level, history of hypertension, and use of angiotensin-converting enzyme inhibitors and beta-blockers. Higher LF and TP preceded early left ventricular dilatation after myocardial infarction.

Lower mortality in patients with the DD genotype of the angiotensin-converting enzyme gene after acute myocardial infarction.

Objective — The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with different serum ACE concentrations and cardiac ACE activity.We assessed whether the ACE gene I/D polymorphism influenced cardiac mortality in Japanese patients with acute myocardial infarction. Methods and results — The ACE gene I/D polymorphism was determined in 441 consecutive patients with a first myocardial infarction.There were 69 patients (16%) with the DD genotype, 194 patients (44%) with the ID genotype, and 178 patients (40%) with the II genotype. During a mean follow-up of 9.4 months, there were 49 cardiac deaths (DD, n = 4; ID, n = 26; II, n = 19).The DD genotype was significantly associated with a lower mortality than the other genotypes (p = 0.0363) by Cox regression analysis adjusted for age, sex, site of myocardial infarction, Killip functional class, reperfusion therapy during acute phase, ACE inhibitor use, and beta-blocker use. Conclusions — In a selected cohort of Japanese patients, the DD genotype was associated with a significantly lower cardiac mortality after a first myocardial infarction.

Higher heart rate variability of smokers after acute myocardial infarction

Although cigarette smoking is known to be a strong risk factor for the development of coronary artery disease, several large clinical studies have demonstrated that current smokers had a favorable prognosis compared to nonsmokers after myocardial infarction. This study sought to evaluate the effect of smoking status on heart rate variability after onset of acute myocardial infarction. We studied 52 patients (34 smokers, 18 nonsmokers) with a first myocardial infarction within 24 h of onset. We recorded 24-h ambulatory ECG to calculate very low frequency power (VLF), low frequency power (LF) and high frequency power (HF) 14 days after onset. Although smokers had a tendency to be younger than nonsmokers (mean age 57 versus 62, P = 0.0812), clinical characteristics were not statistically different between smokers and nonsmokers. After adjustment for age, left ventricular ejection fraction, history of diabetes, acute revascularization and use of beta-blockers, VLF (P = 0.0183) of smokers 14 days after onset was significantly higher than for nonsmokers. In conclusion, although smoking reduces heart rate variability in the general population, higher heart rate variability was observed in smokers than nonsmokers after acute myocardial infarction under the condition of smoking cessation.