Masahiko Moriguchi

Prognostic Utility of B-Type Natriuretic Peptide Assessment in Stable Low-Risk Outpatients With Nonischemic Cardiomyopathy After Decompensated Heart Failure

OBJECTIVES We investigated the clinical utility of B-type natriuretic peptide (BNP) assay in stable outpatients with nonischemic dilated cardiomyopathy (NICM) after decompensated heart failure (HF). BACKGROUND Patients with NICM admitted for decompensated HF frequently experience sudden death or redecompensation after hospital discharge. The prognostic value of BNP during hospitalization has been demonstrated. However, clinical utility of BNP in stable outpatient setting has been poorly investigated. METHODS Eighty-three NICM outpatients who were clinically stable in New York Heart Association functional class 1 to 2 for 6 months after discharge for decompensated HF were enrolled, and then followed for an additional 18 months. The main end point was first readmission for decompensated HF or death. B-type natriuretic peptide levels were measured at 3-month intervals from discharge to enrollment, and echocardiographic dimensions at discharge and enrollment. RESULTS Mean discharge BNP level was 210 +/- 148 pg/ml. Twenty-eight patients were readmitted for decompensated HF or suddenly died at a median time of 11 months from the time of discharge. Among various variables including BNP measurements, clinical parameters and echocardiographic dimensions, a 6-month post-discharge BNP of >190 pg/ml was most closely associated with combined event in the Cox proportional hazards model (hazard ratio 2.29; 95% confidence interval 1.42 to 3.56; p = 0.0005), and had the best discriminatory power (area under the receiver operating characteristic curve 0.91, sensitivity 96%; specificity 76%). CONCLUSIONS Even in stable low-risk outpatients with NICM at 6 months after hospital discharge for decompensated HF, BNP assessment predicts a long-term risk of redecompensation.

Verapamil Suppresses the Inhomogeneity of Electrical Remodeling in a Canine Long‐Term Rapid Atrial Stimulation Model

Verapamil is known to suppress shortening of the atrial effective refractory period (AERP) during relatively short‐term atrial pacing, although the effect of a long‐term stimulation model is unclear. The effect of verapamil on electrical remodeling was evaluated in a canine rapid atrial stimulation model. The right atrial appendage (RAA) was continuously paced (400 beats/min) for 2 weeks. Four pairs of electrodes were sutured at four atrial sites; the RAA, right atrium close to the inferior vena cava, Bachmanns bundle, and LA. AERP, AERP dispersion (AERPd), conduction time, and inducibility of AF were evaluated during the pacing phase and the recovery phase. The same protocol was performed under the administration of verapamil. In five control dogs, the AERP shortening was inhomogeneous and the shortening of the AERP was most prominent in the LA. AERPd increased during the rapid pacing phase by 5 ± 2 ms, but recovered quickly in the recovery phase. The max AERPd was 46 ± 4 ms in the control group and was larger than that in the verapamil group (31 ± 3 ms, P = 0.001). At the LA site, the shortening of the AERP was decreased by verapamil administration (−19 ± 3 vs −5 ± 2 ms, P = 0.04). However, the AF inducibility was not significantly different between the two groups. The effect of verapamil on electrical remodeling was inhomogeneous, depending on the anatomic portion. As a result, AERPd widening during the rapid pacing phase was suppressed by verapamil, while the AF inducibility was unchanged. (PACE 2003; 26:2072–2082)

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.

Effect of procainamide on the postrepolarization refractoriness in cardiac muscle: evaluation using the block coupling interval in the artificial isthmus model in the canine right atrium.

YOSHIZAWA, N., et al.: Effect of Procainamide on the Postrepolarization Refractoriness in Cardiac Muscle: Evaluation Using the Block Coupling Interval in the Artificial Isthmus Model in the Canine Right Atrium. The post‐repolarization refractoriness (PRR) is an important factor to determine the conduction block in cardiac muscle. Recently, we proposed the block coupling interval (BCI) as an useful electrophysiological index for evaluating the PRR. In the present study, the effect of procainamide on PRR was evaluated using the BCI and the effective refractory period (ERP). In five beagle dogs, radiofrequency linear ablation was performed on the right atrial surface parallel to the AV groove, forming an artificial isthmus (8–10 mm width and 15–20 mm length). Bipolar recordings were performed in the isthmus at a resolution of 1.2 mm and single extrastimuli with eight basic drive trains were delivered to cause conduction blocks in the isthmus. When a conduction block occurred, the recorded coupling interval at the recording site just proximal to the site of block was defined as BCI. At the site of the block, the ERP and duration of the monophasic action potential (MAP) at each drive cycle length was measured. The PRR was calculated using two different formulas: (1) [ERP – MAP] and (2) [BCI – MAP]. Procainamide was administrated intravenously at a dose of 15 mg/kg after the control study and the whole study protocol was repeated. The site of the block in an individual dog was always the same. BCI, ERP, and MAP were all shortened in accordance with the shortening of the basic drive cycle length, and the BCI was always the longest, ERP the middle, and the MAP was the shortest. The administration of procainamide prolonged each parameter, but the order of BCI > ERP > MAP remained unchanged. The PRR calculated as [BCI – MAP] was prolonged from 15 ± 10 ms to 29 ± 8 ms by the administration of procainamide (P = 0.048), but [ERP – MAP] was unchanged (8 ± 10 ms vs 8 ± 4 ms). In the conduction block model in the canine right atrium, procainamide prolonged the [BCI – MAP], but did not change the [ERP – MAP]. The procainamide effect of prolonging the PRR might be expressed better by the change in the BCI than the ERP.

Morphological Properties of Atrial Fibrillation Waves in Patients with Left Ventricular Dysfunction —Spectral Analysis of Atrial Fibrillation Waves in Dilated Cardiomyopathy—

Introduction: Although the atrial fibrillation cycle length (FCL) is considered to shorten in persistent atrial fibrillation (AF) as a result of electrical remodeling, whether a long‐term change remains in FCL in patients with left ventricular (LV) dysfunction is uncertain. Morphological properties of AF waves were analyzed in patients with dilated cardiomyopathy (DCM). Methods and Results: The study population consisted of 43 patients with persistent AF, and they were divided into a DCM group (n = 14) and a control group (n = 29). Fibrillation waves from surface ECG lead V1 were purified by subtracting the QRS‐T complex template. Power spectral analysis was performed by Fast Fourier Transformation, and the mean FCL was determined by the peak power frequency in 20 epochs at each recording. The LV ejection fraction was lower in the DCM group (50 ± 18%) than the control (63 ± 8%, p = 0.001). The mean FCL was shorter in the DCM group (132 ± 14 ms) than the control (151 ± 23 ms, p = 0.007) and there was a significant correlation between the FCL and LV dimensions (p = 0.03). Conclusion: In patients with persistent AF and LV dysfunction, FCL was shorter in comparison with the control, and seemed to be influenced by LV dimensions.

ENHANCEMENT OF EARLY DIASTOLIC FILLING PROVOKED BY DOBUTAMINE INFUSION IN DILATED CARDIOMYOPATHY

In considering whether to extend β-blocker therapy to dilated cardiomyopathy, we encountered a valuable case. A 40-year-old man with dilated cardiomyopathy developed heart failure with quite poor systolic function. After administration of β-blocker, his pump function improved. In echocardiographic monitoring before β-blocker therapy, only his early diastolic filling velocity was very responsive to dobutamine loading among functional parameters, including the systolic phase. This finding supports the hypothesis that the enhancement of left ventricular filling by dobutamine loading is a useful predictor in dilated cardiomyopathy patients of whether β-blocker will be effective or not.