Myocardial positron emission computed tomographic images obtained with fluorine-18 fluoro-2-deoxyglucose predict the response of idiopathic dilated cardiomyopathy patients to beta-blockers

Hasegawa, Shin; Kusuoka, Hideo; Maruyama, K.; Hori, Masatsugu; Hatazawa, Jun

doi:10.1016/j.jacc.2003.09.025

Cited by 24 publications

(17 citation statements)

References 22 publications

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“…A number of clinical studies have strongly indicated the link between insulin resistance and nonischemic HF (23)(24)(25)(26). Approximately two-thirds of patients with essential hypertension have abnormal glucose metabolism (27), and there is a positive relationship between cardiac hypertrophy and the plasma insulin concentration (28), suggesting that elevation of insulin contributes to myocardial growth in the presence of chronic pressure overload.…”

Section: Discussionmentioning

confidence: 99%

Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents

Shimizu¹,

Minamino²,

Toko³

et al. 2010

J. Clin. Invest.

200

169

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Although many animal studies indicate insulin has cardioprotective effects, clinical studies suggest a link between insulin resistance (hyperinsulinemia) and heart failure (HF). Here we have demonstrated that excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents. Chronic pressure overload induced hepatic insulin resistance and plasma insulin level elevation. In contrast, cardiac insulin signaling was upregulated by chronic pressure overload because of mechanical stretch-induced activation of cardiomyocyte insulin receptors and upregulation of insulin receptor and Irs1 expression. Chronic pressure overload increased the mismatch between cardiomyocyte size and vascularity, thereby inducing myocardial hypoxia and cardiomyocyte death. Inhibition of hyperinsulinemia substantially improved pressure overloadinduced cardiac dysfunction, improving myocardial hypoxia and decreasing cardiomyocyte death. Likewise, the cardiomyocyte-specific reduction of insulin receptor expression prevented cardiac ischemia and hypertrophy and attenuated systolic dysfunction due to pressure overload. Conversely, treatment of type 1 diabetic mice with insulin improved hyperglycemia during pressure overload, but increased myocardial ischemia and cardiomyocyte death, thereby inducing HF. Promoting angiogenesis restored the cardiac dysfunction induced by insulin treatment. We therefore suggest that the use of insulin to control hyperglycemia could be harmful in the setting of pressure overload and that modulation of insulin signaling is crucial for the treatment of HF.

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Section: Discussionmentioning

confidence: 99%

Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents

Shimizu¹,

Minamino²,

Toko³

et al. 2010

J. Clin. Invest.

200

169

View full text Add to dashboard Cite

show abstract

“…It is thought that these effects are perhaps the most important reasons for the beneficial effects of long-term β-blocker treatment in patients with CHF and coronary heart disease. Indeed, it has been shown that estimation of glucose metabolism may select good responders to β-blocker treatment [18]. The aim of the present study was to establish whether central inhibition of sympathetic activity can produce additional similar changes in myocardial metabolism.…”

Section: Effects On Myocardial Metabolismmentioning

confidence: 91%

Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine

Mobini

Jansson

et al. 2006

Clinical Science

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Although beta-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching placebo. Haemodynamics, NA kinetics and myocardial metabolism were studied over a 2.5 h time period. There was a significant reduction in pulmonary and systemic arterial pressures, together with a decrease in cardiac index in the moxonidine group. Furthermore, there was a simultaneous reduction in systemic and cardiac net spillover of NA in the moxonidine group. Analysis of myocardial consumption of substrates in the moxonidine group showed a significant increase in non-esterified fatty acid consumption and a possible trend towards an increase in myocardial oxygen consumption compared with the placebo group (P=0.16). We conclude that a single dose of moxonidine (0.6 mg) in patients already treated with a beta-blocker reduced cardiac and overall sympathetic activity. The finding of increased lipid consumption without decreased myocardial oxygen consumption indicates a lack of positive effects on myocardial metabolism under these conditions. We suggest this might be a reason for the failure of moxonidine to prevent deaths in long-term studies in CHF.

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“…The potent adrenergic-blocking medication carvedilol, the only beta-blocker approved for HF that does not worsen insulin resistance, is 3 times as likely to cause a dramatic improvement in left ventricular function in the nonischemic cardiomyopathy population as in the ischemic cardiomyopathy population (32). Intriguingly, this degree of response to antiadrenergic therapy can be predicted by the severity of baseline abnormalities in myocardial glucose uptake (33).…”

Section: Clinical Evidencementioning

confidence: 99%

Insulin-Resistant Cardiomyopathy

Witteles

Fowler

2008

Journal of the American College of Cardiology

323

119

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Increasing evidence points to insulin resistance as a primary etiologic factor in the development of nonischemic heart failure (HF). The myocardium normally responds to injury by altering substrate metabolism to increase energy efficiency. Insulin resistance prevents this adaptive response and can lead to further injury by contributing to lipotoxicity, sympathetic up-regulation, inflammation, oxidative stress, and fibrosis. Animal models have repeatedly demonstrated the existence of an insulin-resistant cardiomyopathy, one that is characterized by inefficient energy metabolism and is reversible by improving energy use. Clinical studies in humans strongly support the link between insulin resistance and nonischemic HF. Insulin resistance is highly prevalent in the nonischemic HF population, predates the development of HF, independently defines a worse prognosis, and predicts response to antiadrenergic therapy. Potential options for treatment include metabolic-modulating agents and antidiabetic drugs. This article reviews the basic science evidence, animal experiments, and human clinical data supporting the existence of an "insulin-resistant cardiomyopathy" and proposes specific potential therapeutic approaches.

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Myocardial positron emission computed tomographic images obtained with fluorine-18 fluoro-2-deoxyglucose predict the response of idiopathic dilated cardiomyopathy patients to beta-blockers

Abstract: It has been shown that FDG-PET is a good predictor for the effectiveness of beta-blockers.

Cited by 24 publications

References 22 publications

Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents

Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents

Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine

Insulin-Resistant Cardiomyopathy

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