Mechanisms of Carvedilol Action in Human Congestive Heart Failure

Kaye, David M.; Johnston, Leonie; Vaddadi, Gautam; Brunner‐LaRocca, Hans‐Peter; Jennings, Garry; Esler, Murray

doi:10.1161/01.hyp.37.5.1216

Cited by 17 publications

(13 citation statements)

References 43 publications

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“…By virtue of the invasive nature of our study, the sample size in this study is relatively modest, limiting the statistical power of our conclusions. The cohort size is however similar to previous studies investigating cardiac neurohormonal responses to hemodynamic interventions 12,25–27 …”

Section: Limitationssupporting

confidence: 63%

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Atrial Fibrillation Is Associated with Decreased Cardiac Sympathetic Response to Isometric Exercise in CHF in Comparison to Sinus Rhythm

Gould¹,

Esler

Kaye³

2008

Pacing Clinical Electrophis

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In this study, we demonstrate for the first time that the combination of AF and CHF is accompanied by a marked attenuation of the cardiac sympathetic response to acute hemodynamic stress. This implies AF is associated with a further impairment of baroreceptor response in CHF compared to SR. These findings present possible insights to the associated increased mortality and pathogenesis of AF with CHF.

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Section: Limitationssupporting

confidence: 63%

“…The cohort size is however similar to previous studies investigating cardiac neurohormonal responses to hemodynamic interventions. 12,[25][26][27]…”

Section: Limitationsmentioning

confidence: 99%

Atrial Fibrillation Is Associated with Decreased Cardiac Sympathetic Response to Isometric Exercise in CHF in Comparison to Sinus Rhythm

Gould¹,

Esler

Kaye³

2008

Pacing Clinical Electrophis

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“…These two parameters are not influenced by carvedilol [25]. These findings suggest that the principal mode of action of β‐blockade in heart failure is probably mediated by protection against the toxic effects of catecholamines on the heart [26].…”

Section: Discussionmentioning

confidence: 73%

Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure

Castro

Vukasovic

Chiong

et al. 2005

European J of Heart Fail

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Background: Our previous studies suggest that the increase in heart rate from rest to peak exercise is reduced in patients with chronic heart failure (CHF) and this is associated with increased oxidative stress, as determined by malondialdehyde (MDA) plasma levels. Aim: To investigate the effects of carvedilol on the heart rate response to exercise and oxidative stress in patients with CHF. Methods and results: Thirty stable NYHA classes II-III CHF patients received carvedilol therapy for 6 months, at a mean maintenance dose of 25 mg (range 6.25-50 mg/day). After treatment, the patients showed a significant improvement in their functional NYHA class ( p=0.013), increased left ventricular ejection fraction (LVEF) (24F1.4% to 31F2.3%, p=0.003) and 6-min walk distance (499F18 to 534F18 m, p=0.03), without changes in the peak VO 2 . At baseline, norepinephrine (NE) plasma levels increased with exercise (510F51 to 2513F230 pg/mL, pb0.001), and these levels were not affected by carvedilol. Chronotropic responsiveness index (increase in heart rate divided by the increase in NE from rest to peak exercise) was not changed by carvedilol (0.049F0.001 to 0.042F0.001, p=0.6). MDA levels of CHF patients decreased after treatment with carvedilol (2.4F0.2 to 1.1F0.2 AM, pb0.001), without changes in antioxidant enzyme activities. Conclusions: Carvedilol treatment in patients with CHF results in reduced oxidative stress without restoration of the chronotropic responsiveness index.

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“…[20][21][22][23][24] The reported benefits of b-blocker therapy are owing to a complex combination of events, including restoration of b-receptor signaling, myocardiocyte protection against oxidative stress and apoptosis, mitigation of cyclic adenosine monophosphate (cAMP)-induced hyperphosphorylation, improved Ca 2+ cycling, and improved efficiency of myocardial energetics. 11,12,[25][26][27] The results of the present study may be due to differences in the severity, progression, and differing etiology of canine and human DCM, inadequate drug dosages, and the brevity of follow-up.…”

Section: Discussionmentioning

confidence: 84%

Carvedilol in Dogs with Dilated Cardiomyopathy

et al. 2007

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Background: Dilated cardiomyopathy (DCM) is characterized by reduced systolic function, heightened sympathetic tone, and high morbidity and mortality. Little is known regarding the safety and efficacy of b-blocker treatment in dogs with DCM.Hypothesis: Carvedilol improves echocardiographic and neurohormonal variables in dogs with DCM over a 4-month treatment period.Methods: Prospective, placebo-controlled, double-blinded randomized study. Dogs with DCM underwent echocardiography, ECG, thoracic radiographs, and neurohormonal profiling, followed by titration onto carvedilol (0.3 mg/kg q12h) or placebo over a 4-week period and subsequently received 3 months of therapy. Primary study endpoints included left ventricular volume and function.Results: Sixteen dogs received carvedilol and 7 received placebo. At study end, 13 carvedilol dogs and 5 placebo dogs were alive. There was no difference in the mean percentage change in left ventricular volume at end-diastole (LVVd), left ventricular end-systolic volume (LVVs), and ejection fraction (EF) between treatment groups, suggesting that both groups experienced similar amounts of disease progression. Carvedilol treatment did not result in significant changes in neurohormonal activation, radiographic heart size, heart rate, or owner perceived quality-of-life. Baseline B-type natriuretic peptide (BNP) predicted dogs in the carvedilol-treated group that maintained or improved their EF over the study duration.Conclusions and Clinical Importance: Carvedilol administration did not improve echocardiographic or neurohormonal indicators of heart function. The lack of effect may be related to severity of disease, carvedilol dose, or brevity of follow-up time. Statistical power of the present study was adversely affected by a high fatality rate in study dogs and small sample size.

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Mechanisms of Carvedilol Action in Human Congestive Heart Failure

Cited by 17 publications

References 43 publications

Atrial Fibrillation Is Associated with Decreased Cardiac Sympathetic Response to Isometric Exercise in CHF in Comparison to Sinus Rhythm

Atrial Fibrillation Is Associated with Decreased Cardiac Sympathetic Response to Isometric Exercise in CHF in Comparison to Sinus Rhythm

Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure

Carvedilol in Dogs with Dilated Cardiomyopathy

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