Yukihiko Abe

Acute heart failure volume control multicenter randomized (AVCMA) trial: comparison of tolvaptan and carperitide.

Acute decompensated heart failure (ADHF) is a common and highly morbid cardiovascular disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide.

Vasopressin V2 receptor antagonist tolvaptan is effective in heart failure patients with reduced left ventricular systolic function and low blood pressure.

Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. Carperitide has natriuretic and vasodilatory effects, and tolvaptan produces water excretion without electrolyte excretion. We previously reported the usefulness of tolvaptan compared to carperitide in ADHF patients with fluid volume retention. The purpose of this study was to examine whether the efficacy of tolvaptan was altered in ADHF patients with reduced left ventricular systolic function and in those with hypotension. A total of 109 hospitalized ADHF patients were randomly assigned to either a tolvaptan or a carperitide treatment group. Baseline clinical characteristics were not different between the two groups. We divided these patients based on the left ventricular ejection fraction (EF) by echocardiography, and blood pressure (BP) at the time of admission. Daily urine volume between the tolvaptan and carperitide groups in patients with preserved EF (≥ 50%) was not different, however, in those with reduced EF (< 50%), the urine volume was significantly higher in the tolvaptan group than in the carperitide group (day 2, 3, 4, P < 0.05 for all). Daily urine volume did not differ between these two groups in the high blood pressure group (BP ≥ 140 mmHg), but was significantly higher in the tolvaptan group than in the carperitide group (day 1, P = 0.021; day 3, P = 0.017) in the low blood pressure group (BP < 140 mmHg). The present study reveals that tolvaptan is more effective than carperitide, especially in ADHF patients with reduced left ventricular systolic function and without hypertension.

Long-Term Effects and Prognosis in Acute Heart Failure Treated with Tolvaptan: The AVCMA Trial

Background. Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. We previously reported the efficacy and safety of tolvaptan compared to carperitide in hospitalized patients with ADHF. There were some reports of cardio- and renal-protective effects in carperitide; therefore, the purpose of this study was to compare the long-term effects of tolvaptan and carperitide on cardiorenal function and prognosis. Methods and Results. One hundred and five ADHF patients treated with either tolvaptan or carperitide were followed after hospital discharge. Levels of plasma B-type natriuretic peptide, serum sodium, potassium, creatinine, and estimated glomerular filtration rate were measured before administration of tolvaptan or carperitide at baseline, the time of discharge, and one year after discharge. These data between tolvaptan and carperitide groups were not different one year after discharge. Kaplan-Meier survival curves demonstrated that the event-free rate regarding all events, cardiac events, all cause deaths, and rehospitalization due to worsening heart failure was not significantly different between tolvaptan and carperitide groups. Conclusions. We demonstrated that tolvaptan had similar effects on cardiac and renal function and led to a similar prognosis in the long term, compared to carperitide.

Unstimulated polymorphonuclear neutrophils regulate proximal coronary arterial tone

Our objective is to clarify, by measuring the superoxide production as a marker of inactive state of polymorphonuclear neutrophils, whether unstimulated polymorphonuclear neutrophils would influence coronary arterial tone. We recorded the isometric tension of the porcine coronary arterial ring in a bath of oxygenated Krebs Ringer solution. Unstimulated porcine polymorphonuclear neutrophils that contained little superoxide were added to the bath. We also analyzed the prostaglandins produced in the bath. The isometric tension of arterial rings increased dose-dependently when polymorphonuclear neutrophils were added to the bath. The vasoconstriction induced by unstimulated polymorphonuclear neutrophils was inhibited by endothelial denudation, indomethacin, anti-CD11a/18-like antibody. Thromboxane A2 synthetase inhibitor and superoxide dismutase did not effect the vasoconstriction. Prostaglandin E2 predominated among the prostaglandins produced in the bath; its production was significantly inhibited by indomethacin (without vs. with indomethacin; 3898 +/- 1704 vs 1956 +/- 715 pg/ml, P < 0.05, n=6). Pretreatment of vascular rings with indomethacin blocked the interaction of the coronary artery with polymorphonuclear neutrophils. Results suggested that unstimulated polymorphonuclear neutrophils constrict the proximal coronary artery. Such vasoconstriction may be produced by cyclooxygenase products, especially prostaglandin E2 produced in the vascular wall via the interaction between the polymorphonuclear neutrophils and the endothelium. Polymorphonuclear neutrophils may regulate coronary arterial tone.

Paradoxical Response of Epicardial Coronary Arteries and Small Resistance Vessels to Intracoronary Acetylcholine in Vasospastic Angina

This study was carried out to examine the response of epicardial arteries (A-epi) and small resistance vessels (A-res) to intracoronary (IC) acetylcholine (Ach) in patients with and without vasospastic angina. Injection of Ach (20, 50 μg) into the left coronary artery (LCA) was performed in ten patients whose LCAs were angiographically normal. Ach-induced spasm of the left anterior descending artery (LAD) occurred in five patients (group A), and did not occur in the other five (group B). We injected nitroglycerin (NTG; 0.2 mg) into the LCA to remove A-epi tone, followed by the same amount of Ach to evaluate the response of A-res. Thereafter, papaverine (10 mg) was injected into the LCA to evaluate the maximum vasodilation capacity. Flow in the great cardiac vein, measured by Webster’s method, and coronary angiography were performed following the IC injection of each drug. We calculated the coronary vascular resistance ratio (R) to maximum dilator response and measured LAD diameter after each procedure. Percent changes in LAD diameter after IC Ach following IC NTG did not differ in the two groups. The R(NTG)-R(Ach) value was larger in group A than in group B (0.35 ± 0.1 vs 0.12 ± 0.1; P < 0.01). These findings suggest that IC injection of Ach produces significant vasodilation in A-res in vasospastic angina, in contrast to the constriction produced in A-epi by this treatment.