Comparative Left Ventricular Functional and Neurohumoral Effects of Chronic Treatment With Carvedilol Versus Metoprolol in Patients With Dilated Cardiomyopathy

Hirooka, Keiji; Yasumura, Yoshio; Ishida, Yoshiteru; Hanatani, Akihisa; Nakatani, Satoshi; Komamura, Kazuo; Hori, Masatsugu; Yamagishi, Masakazu; Miyatake, Kunio

doi:10.1253/jcj.65.931

Cited by 27 publications

(10 citation statements)

References 28 publications

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“…4,12 The mechanisms of the beneficial effects of -blockers on heart failure include suppression of oxygen consumption, upregulation of -adrenergic receptors, antiarrhythmic effects, reduction of cardiac norepinephrine and improvement of ventricular diastolic function. [13][14][15] Carvedilol is a potent non-selective -blocker, with an additional vasodilating effect related to 1 adrenergic receptor blockade. The drug also has antioxidant effects 11 and has recently been considered as a primary drug for the treatment of chronic heart failure.…”

Section: Discussionmentioning

confidence: 99%

Beta-Blocker Therapy for Cardiac Dysfunction in Patients With Muscular Dystrophy

Kajimoto

Ishigaki

Okumura

et al. 2006

Circ J

102

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eart failure is one of the major causes of death in patients with Duchenne muscular dystrophy (DMD). 1 It has been shown that angiotensin-converting enzyme inhibitors (ACEI) and -blockers effectively improve symptoms and cardiac function, and decrease mortality in adult patients with congestive heart failure caused by ischemic heart disease or dilated cardiomyopathy. 2-5 However, whether these drugs are effective in the management of patients with muscular dystrophy has not been well studied. We investigated whether a -blocker, carvedilol, in addition to an ACEI is effective to improve cardiac function in patients with muscular dystrophy. Methods PatientsBetween August 1999 and December 2002, 28 patients, age 17±5 years (range 7-29 years), were started on cilazapril or enalapril because of ventricular dysfunction. Diagnoses were DMD in 25 patients; Fukuyama-type muscular dystrophy in 2 patients, and Emery-Dreifuss muscular dystrophy in 1. The decision to start an ACEI was based on echocardiographic findings; these drugs were started when left Circulation Journal Vol.70, August 2006 ventricular (LV) fractional shortening (FS) was <0.26. After the dosage of the ACEI reached its final value, the 28 patients were randomly allocated into 2 groups: carvedilol plus an ACEI (carvedilol group: 13 patients; age 18±6 years, range 7-27 years), or an ACEI only (ACEI group: 15 patients; age 15±4 years, range 8-29 years).Because all patients were physically not active, it was difficult to evaluate cardiac symptoms, so in the present study, they were considered to be present if patients complained of fatigue, palpitations, sweating, and/or chest discomfort.There were no significant differences in age, body weight, the ratio of patients with cardiac symptoms, ratio of patients with concomitant use of diuretics, heart rate, blood pressure, and plasma brain natriuretic peptide (BNP) levels between the 2 groups before drug administration (Tables 1,2 Background In muscular dystrophy, cardiac function deteriorates with time and heart failure is one of the major causes of death. Although the combination of angiotensin-converting enzyme inhibitors (ACEI) and -blockers improves cardiac function in adults, little is known about the efficacy of those drugs in patients with muscular dystrophy. Methods and ResultsThe effect of the -blocker, carvedilol, and/or ACEI on ventricular function in patients with muscular dystrophy was studied. Carvedilol and an ACEI were given to 13 patients (ACEI group; mean age 18 years, range 7-27 years), and an ACEI only to 15 patients (carvedilol group; mean age 15 years, range 8-29 years). Diagnoses included Duchenne muscular dystrophy (n=25), Fukuyama muscular dystrophy (n=2), and Emery-Dreifuss muscular dystrophy (n=1). Echocardiographic parameters of the left ventricle were measured during the 2-3 years of follow-up. In the carvedilol group, combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS). In the ACEI group, th...

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Section: Discussionmentioning

confidence: 99%

Beta-Blocker Therapy for Cardiac Dysfunction in Patients With Muscular Dystrophy

Kajimoto

Ishigaki

Okumura

et al. 2006

Circ J

102

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“…Up to 20 mg of carvedilol is considered to be tolerable in most Japanese patients with heart failure. 30 Carvedilol at a dose of 10 to 20 mg once daily is considered to be an effective and safe treatment for Japanese patients with essential hypertension. 31 Therefore, the mean dose in this study was not too low for Japanese patients with heart failure.…”

Section: Discussionmentioning

confidence: 99%

Carvedilol Decreases Elevated Oxidative Stress in Human Failing Myocardium

et al. 2002

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Background-Oxidative stress has been implicated in the pathogenesis of heart failure. However, direct evidence of oxidative stress generation in the human failing myocardium has not been obtained. Furthermore, the effect of carvedilol, a vasodilating ␤-blocker with antioxidant activity, on oxidative stress in human failing hearts has not been assessed. This study was therefore designed to determine whether levels of lipid peroxides are elevated in myocardia of patients with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid peroxidation level. Methods and Results-Endomyocardial biopsy samples obtained from 23 patients with DCM and 13 control subjects with normal cardiac function were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation product. Expression of HNE-modified protein was found in all myocardial biopsy samples from patients with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial HNE-modified protein levels in patients with DCM were significantly increased compared with the levels in control subjects (PϽ0.0001). Endomyocardial biopsy samples from 11 patients with DCM were examined before and after treatment (mean, 9Ϯ4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22Ϯ8 mg/d). After treatment with carvedilol, myocardial HNE-modified protein levels decreased by 40% (PϽ0.005) along with amelioration of heart failure. Conclusions-Oxidative stress is elevated in myocardia of patients with heart failure. Administration of carvedilol resulted in a decrease in the oxidative stress level together with amelioration of cardiac function.

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“…LV dilatation after AMI is one of the key characteristics of LVRM 13 and is the most powerful predictor of poor prognosis. 14 So the attenuation of LV dilatation by carvedilol is of clinical significance because it indicates that carvedilol not only can be used for the treatment of heart failure, as demonstrated in clinical studies, 5,15,16 but also can probably be used to prevent heart failure via the attenuating of LV dilatation after AMI. 6 Hypertrophy of the non-infarcted myocardium is the main pathologic basis of LVRM and is initiated and promoted by hemodynamic abnormality and activation of the SNS and RAS.…”

Section: Effect Of Carvedilol and Losartan Alone And In Combination Omentioning

confidence: 99%

Comparative Effects of Carvedilol and Losartan Alone and in Combination for Preventing Left Ventricular Remodeling After Acute Myocardial Infarction In Rats

Yang

Tang

Ruan

et al. 2003

Circ J

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t is well known that left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) plays a very important role in progressive left ventricular (LV) dysfunction and subsequent heart failure. It is characterized by infarct expansion, hypertrophy of the noninfarcted myocardium and alteration of LV geometry, and manifests as progressive LV dilatation. Experimental studies have shown that angiotensin II type I (AT1) receptor antagonists, such as losartan, is beneficial in attenuating post-infarction LVRM. 1-4 Carvedilol, a third-generationblocker, is a unique, multiaction drug with non-selectiveblockade, 1-blockade and antioxidant effects. Clinical studies have shown that carvedilol is beneficial in preventing LVRM in patients with ischemic heart failure. 5,6 Therefore, we hypothesized that carvedilol should be effective, Circulation Journal Vol.67, February 2003 and its combination with losartan should be superior, in preventing post-infarction LVRM. So, the purpose of this study was to compare the effects of carvedilol and losartan alone and in combination on LVRM after AMI in rats. Methods Experimental Rats and GroupsAMI as induced by ligating the left coronary artery in 133 female Sprague-Dawley (SD) rats (body weight: 200-250 g). At 24 h after the operation, the 100 surviving rats were randomized to 4 groups: (1) AMI controls (n=25), (2) carvedilol (1 mg·kg -1 ·d -1 , n=25), (3) losartan (3 mg·kg -1 ·d -1 , n=25), and (4) carvedilol (1 mg·kg -1 ·d -1 ) + losartan (3 mg · kg -1 · d -1 ) (combination, n=25) groups. Sham-operated rats (n=17) were randomly selected before the AMI operation. MethodsAMI was conducted by a method previously reported by Olivetti et al. 7 After anaesthesia with ketamine (30 mg/kg) and diazepam (5 mg/kg), and then a thoracotomy, the left coronary artery of each rat was ligated using a 6-0 prolene suture, which induced an anterior myocardial infarction. In It has been verified that losartan has beneficial effects on ventricular remodeling (VRM) after acute myocardial infarction (AMI), but the effects of carvedilol alone or in combination with losartan on this condition have not been defined. The present study used rats to compare the effects of carvedilol and losartan alone and in combination for preventing VRM after AMI. After ligation of the left coronary artery, 100 surviving female SpragueDawley rats were randomly assigned to 1 of 4 groups: (1) AMI control (n=25), (2) carvedilol (Car, 1 mg·kg -1 · day -1 ) (n=25), (3) losartan (Los, 3 mg·kg -1 ·day -1 ) (n=25), and (4) Car (1 mg·kg -1 ·day -1 ) + Los (3 mg·kg -1 · day -1 ) (n=25). A sham-operated group (n=17) was also randomly selected. Drugs were administered by gastric gavage for 4 weeks. After hemodynamic studies, the hearts were fixed and analyzed pathologically. Exclusive of the rats that had died or had an infarct size <35% or >55%, complete data were obtained for 65 rats, comprising AMI control (n=13), Car (n=12), Los (n=13), combination (n=14), and sham (n=13)

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Comparative Left Ventricular Functional and Neurohumoral Effects of Chronic Treatment With Carvedilol Versus Metoprolol in Patients With Dilated Cardiomyopathy

Cited by 27 publications

References 28 publications

Beta-Blocker Therapy for Cardiac Dysfunction in Patients With Muscular Dystrophy

Beta-Blocker Therapy for Cardiac Dysfunction in Patients With Muscular Dystrophy

Carvedilol Decreases Elevated Oxidative Stress in Human Failing Myocardium

Comparative Effects of Carvedilol and Losartan Alone and in Combination for Preventing Left Ventricular Remodeling After Acute Myocardial Infarction In Rats

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