Michiro Kiryu

Prognostic Significance of Frequent Premature Ventricular Contractions Originating from the Ventricular Outflow Tract in Patients with Normal Left Ventricular Function.

Background: Recently, it has been reported that frequent premature ventricular contractions (PVCs) may be associated with causing heart failure in patients with left ventricular (LV) dysfunction. However, the prognostic significance of frequent PVCs in asymptomatic patients with a normal LV function is unclear. Methods: Two hundred and thirty-nine consecutive patients presenting with frequent PVCs (>1000 beats/day) originating from the right or left ventricular outflow tract without any detectable heart disease were enrolled in the study. Structural heart disease was ruled out by echocardiography and cardiac magnetic resonance imaging, and Holter-ECG monitoring was repeated two or three times to evaluate the PVC prevalence at the initial evaluation. All patients were followed up for at least 4 years, and further observation was continued if possible. Results: During an observation period of 5.6 (1.7) years, no patients exhibited any serious cardiac events. Although there was no significant change in the mean LV ejection fraction (LVEF) and mean LV diastolic dimension (LVDd), there was a significant negative correlation between the PVC prevalence and ΔLVEF (p<0.001) and positive correlation between the PVC prevalence and ΔLVDd (p<0.001). When the development of LV dysfunction was defined as ΔLVEF>−6%, 13 patients exhibited LV dysfunction. For the prediction of the development of LV dysfunction, PVC prevalence and LVEF at the initial evaluation were independent predicting factors (p<0.01). Conclusion: Although the prognosis in patients with frequent PVCs was considered relatively benign, attention should be paid to the progression of the LV dysfunction during a long-term observation, especially in patients with a high PVC prevalence.

Angiotensin II-mediated up-regulation of connective tissue growth factor promotes atrial tissue fibrosis in the canine atrial fibrillation model

Aims Remodelling of the extracellular matrix (ECM) plays an important role in the production of arrhythmogenic substrate for atrial fibrillation (AF), and is considered to be promoted by the connective tissue growth factor (CTGF). Our objective was to assess the relationship between CTGF and ECM synthesis, and the effect of olmesartan on these processes. Methods and results Fifteen canine AF models were produced by rapid atrial stimulation. They were divided into three groups: pacing control (n = 5): 6-week pacing, pacing + olmesartan (n = 5): pacing with olmesartan (2 mg/kg/day), and non-pacing group (n = 5). In the pacing control group, messenger ribonucleic acid expressions of CTGF and collagen types 1 and 3 were up-regulated in comparison with the non-pacing group (P < 0.05) while transforming growth factor-β (TGF-β) did not exhibit a significant difference. In the pacing + olmesartan group, these up-regulations were suppressed (P < 0.05). In fluorescent immunostaining, the expression of CTGF was localized in the cytoplasm. The protein level of collagen type 3 was increased in the pacing control and it was suppressed in the pacing + olmesartan group. Conclusions CTGF and associated genes were up-regulated in the atria with the appearance of fibrosis. Because this up-regulation was independent of TGF-β and suppressed by olmesartan, CTGF up-regulation was considered to be mediated by angiotensin II.

Combined effects of up- and downstream therapies on atrial fibrillation in a canine rapid stimulation model

BACKGROUND Recent reports suggest angiotensin receptor blockers (ARBs) and some antiarrhythmic agents affect atrial remodeling in atrial fibrillation (AF). We evaluated the effect of combination therapy with olmesartan (Olm) and bepridil (Bep) in a canine model of AF. METHODS AND RESULTS An atrial stimulation device was implanted in 10 dogs undergoing 6-week pacing at 400 bpm. They were divided into Olm (2 mg/kg/day) (n=5) and Olm+Bep (Olm, 2 mg/kg/day; Bep, 10 mg/kg/day) groups (n=5). Atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated weekly, and hemodynamics, atrial histology, and mRNA expression and protein expression of ion-channel and gap junction-related molecules at 6 weeks. Data were compared between groups and with non-pacing control and pacing-control groups from our previous report. The pacing-control group exhibited shortened AERP, decreased CV, increased AF inducibility and tissue fibrosis, and down-regulated L-type Ca(2+) channel (LCC), SCN5A, Kv4.3 and connexin43 (Cx43). By comparison, the Olm group exhibited suppression of the decrease in CV and of the increase in AF inducibility, but no change in AERP shortening. The Olm+Bep group exhibited suppression of AERP shortening as well as the greatest decrease in AF inducibility. Histologically, tissue fibrosis was suppressed in Olm and Olm+Bep groups. Down-regulation of Cx43 was partly suppressed in the Olm group while that of LCC, SCN5A, and Cx43 was suppressed in the Olm+Bep group. CONCLUSION Olm and Bep in combination suppressed AF inducibility more strongly than Olm alone, and may be more useful in the suppression of AF.

Long-term observation of fibrillation cycle length in patients under angiotensin II receptor blocker therapy for chronic atrial fibrillation

The long‐term effect of angiotensin II receptor blockers (ARBs) on atrial fibrillation (AF) is unclear. In this study, we evaluated the change in the fibrillation cycle length (FCL) in patients under long‐term ARB therapy for chronic AF.

Preventive Effect of Amiodarone on VT/VF Events in ICD Patients with Structural Heart Diseases

Background: Although amiodarone (AMD) is applied for implantable cardioverterdefibrillator (ICD) patients to reduce VT/VF events, its actual benefit and long‐term efficacy are unclear. In the present study, we retrospectively evaluated the incidence of VT/VF events in ICD patients with and without AMD.