Impact of 6 months of therapy with carvedilol on muscle sympathetic nerve activity in heart failure patients

Matos, Luciana Diniz Nagem Janot de; Gardenghi, Giulliano; Rondon, Maria Urbana Pinto Brandão; Soufen, Helena Nogueira; A, Tirone; Barretto, Antônio Carlos Pereira; Brum, Patrícia Chakur; Middlekauff, Holly R.; Negräo, Carlos Eduardo

doi:10.1016/j.cardfail.2004.03.006

Cited by 52 publications

(39 citation statements)

References 29 publications

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“…However, these effects, if present, were negligible, because patients served as their own controls in our study design. Furthermore, β-blockers reduce MSNA, 28 and our patients demonstrated marked increases in efferent sympathetic activity despite taking the drug, which furthers our hypothesis that a reduction in pulsatility leads to a baroreceptor-mediated augmentation of the sympathetic nervous system. Approximately half of our patients had a history of ischemic cardiomyopathy, and we cannot rule out the possibility of subclinical peripheral vascular disease among these individuals, which may have influenced carotid arterial distension.…”

Section: Limitationssupporting

confidence: 84%

“…However, it is well known that β-blockers improve outcomes through protection of the heart from the hyperadrenergic environment associated with advanced HF. [25][26][27] Therefore, it is possible that reductions in MSNA, either through β-blockade 28 or increased pulse pressure with future-generation devices, could lead to improved outcomes in this population.…”

Section: Sympathetic Tone After Insertion Of a Cf-lvadmentioning

confidence: 99%

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Restoration of Pulsatile Flow Reduces Sympathetic Nerve Activity Among Individuals With Continuous-Flow Left Ventricular Assist Devices

et al. 2015

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Thirteen patients with implanted Heartmate II CF-LVADs were recruited from the University of Texas Southwestern Medical Center advanced heart failure (HF)/mechanical circulatory support Background-Current-generation left ventricular assist devices provide circulatory support that is minimally or entirely nonpulsatile and are associated with marked increases in muscle sympathetic nerve activity (MSNA), likely through a baroreceptor-mediated pathway. We sought to determine whether the restoration of pulsatile flow through modulations in pump speed would reduce MSNA through the arterial baroreceptor reflex. Methods and Results-Ten men and 3 women (54±14 years) with Heartmate II continuous-flow left ventricular assist devices underwent hemodynamic and sympathetic neural assessment. Beat-to-beat blood pressure, carotid ultrasonography at the level of the arterial baroreceptors, and MSNA via microneurography were continuously recorded to determine steady-state responses to step changes (200-400 revolutions per minute) in continuous-flow left ventricular assist device pump speed from a maximum of 10 480±315 revolutions per minute to a minimum of 8500±380 revolutions per minute. Reductions in pump speed led to increases in pulse pressure (high versus low speed: 17±7 versus 26±12 mm Hg; P<0.01), distension of the carotid artery, and carotid arterial wall tension (P<0.05 for all measures). In addition, MSNA was reduced (high versus low speed: 41±15 versus 33±16 bursts per minute; P<0.01) despite a reduction in mean arterial pressure and was inversely related to pulse pressure (P=0.037). Conclusions-Among subjects with continuous-flow left ventricular assist devices, the restoration of pulsatile flow through modulations in pump speed leads to increased distortion of the arterial baroreceptors with a subsequent decline in MSNA. Additional study is needed to determine whether reduction of MSNA in this setting leads to improved outcomes.

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Section: Limitationssupporting

confidence: 84%

Section: Sympathetic Tone After Insertion Of a Cf-lvadmentioning

confidence: 99%

Restoration of Pulsatile Flow Reduces Sympathetic Nerve Activity Among Individuals With Continuous-Flow Left Ventricular Assist Devices

et al. 2015

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“…Standard life-prolonging neurohormonal blockers for CHF, including ACEIs, ARBs, beta-blockers and aldosterone antagonists, have been shown to improve HRV parameters in patients with CHF (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), and the success in treating CHF by pharmacological neurohumoral antagonists underscores the importance of modulating the neurohumoral axis to improve clinical outcome (37,38).…”

Section: Discussionmentioning

confidence: 99%

The preserved autonomic functions may provide the asymptomatic clinical status in heart failure despite advanced left ventricular systolic dysfunction

Kocaman

Taçoy²,

Özdemir³

et al. 2010

Anadolu Kardiyol Derg

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Objective: Autonomic dysfunction is an important marker of prognosis in congestive heart failure (CHF) and may determine the symptoms and progression of CHF. The aim of our study was to investigate whether preserved autonomic function assessed by heart rate variability (HRV) analyses is related to absence of CHF symptoms despite prominently reduced systolic function. Methods: The study had a cross-sectional observational design. Fifty patients with left ventricular ejection fraction (EF) below 40% were enrolled. The patients were divided into two groups according to their CHF symptomatic status as Group 1 (NYHA functional class I, asymptomatic group) and Group 2 (NYHA functional class≥ II, symptomatic group). Plasma C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-proBNP) levels, echocardiographic parameters and HRV indices were measured while the patients were clinically stable in each group. Possible factors associated with the development of CHF symptoms were assessed by using multiple regression analysis. Results: Baseline clinical characteristics and left ventricular EF were similar in the two groups. Serum CRP (15±21 vs 7±18 mg/L, p=0.011) and NT-proBNP levels (1935±1088 vs 1249±1083 pg/mL, p=0.020) were significantly higher in symptomatic group. The HRV parameters (SDNN: 78±57 vs 122±42 ms, p=0.001; SDANN: 65±55 vs 84±38 ms, p=0.024; SDNNi: 36±41 vs 70±46 ms, p<0.001; triangular index [Ti]: 17±12 vs 32±14, p<0.001) were also significantly depressed in symptomatic group. When multiple regression analysis was performed, only HRV indices of autonomic function were significantly associated with the asymptomatic status (SDNN, OR: 1.016, 95%CI: 1.002-1.031, p=0.028; SDNNi, OR: 1.030, 95%CI: 1.008-1.052, p=0.006; TI, OR: 1.088, 95%CI: 1.019-1.161, p=0.011). Conclusion: Preserved autonomic functions were shown to be associated with absence of CHF symptoms independently of angiotensin converting enzyme inhibitor/angiotensin receptor blocker's treatment and BNP levels and may be protective against the development of CHF symptoms despite advanced left ventricular systolic dysfunction. (Anadolu Kardiyol Derg 2010 December 1; 10(6); 519-25) Key words: Heart rate variability, systolic heart failure, preserved autonomic function, autonomic dysfunction, clinical symptoms, regression analysis ÖZET Amaç: Otonomik disfonksiyon konjestif kalp yetersizliğinde (KKY) prognozun önemli bir belirleyicisidir ve KKY'nin semptomlarını ve ilerlemesini öngörebilir. Çalışmamızın amacı belirgin olarak azalmış sistolik fonksiyonu olan hastalarda kalp hızı değişkenliği (KHD) ile belirlenen korunmuş otonomik fonksiyonun KKY semptomlarının yokluğu ile ilişkili olup olmadığının araştırılmasıdır. Yöntemler: Çalışma gözlemsel ve enine-kesitli olarak planlandı. Sol ventrikül ejeksiyon fraksiyonu (EF) %40'ın altında 50 hasta çalışmaya alındı. Hastalar KKY semptomatik durumlarına göre; Grup 1 (NYHA sınıf I, asemptomatik grup) ve Grup 2 (NYHA sınıf>=II, semptomatik grup) olmak üzere iki gruba ayrıldılar. Hastaların p...

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“…In fact, we have previously observed that carvedilol treatment of HF patients decreases sympathetic activity measured directly by microneurography performed on the peroneal nerve (6). Although β-blockers are known for their positive impact on cardiac function and their ability to reverse remodeling (7), they fail to improve forearm blood flow and overall functional capacity of HF patients (6). However, when β-blocker therapy is associated with exercise training there is an increase in forearm blood flow and exercise capacity (8).…”

Section: Introductionmentioning

confidence: 95%

Effect of exercise training and carvedilol treatment on cardiac function and structure in mice with sympathetic hyperactivity-induced heart failure

Medeiro

Vanzelli

Rosa

et al. 2008

Braz J Med Biol Res

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The present investigation was undertaken to study the effect of β-blockers and exercise training on cardiac structure and function, respectively, as well as overall functional capacity in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α 2A /α 2C ArKO). α 2A /α 2C ArKO and their wild-type controls were studied for 2 months, from 3 to 5 months of age. Mice were randomly assigned to control (N = 45), carvedilol-treated (N = 29) or exercise-trained (N = 33) groups. Eight weeks of carvedilol treatment (38 mg/kg per day by gavage) or exercise training (swimming sessions of 60 min, 5 days/week) were performed. Exercise capacity was estimated using a graded treadmill protocol and HR was measured by tail cuff. Fractional shortening was evaluated by echocardiography. Cardiac structure and gastrocnemius capillary density were evaluated by light microscopy. At 3 months of age, no significant difference in fractional shortening or exercise capacity was observed between wild-type and α 2A / α 2C ArKO mice. At 5 months of age, all α 2A /α 2C ArKO mice displayed exercise intolerance and baseline tachycardia associated with reduced fractional shortening and gastrocnemius capillary rarefaction. In addition, α 2A /α 2C ArKO mice presented cardiac myocyte hypertrophy and ventricular fibrosis. Exercise training and carvedilol similarly improved fractional shortening in α 2A / α 2C ArKO mice. The effect of exercise training was mainly associated with improved exercise tolerance and increased gastrocnemius capillary density while β-blocker therapy reduced cardiac myocyte dimension and ventricular collagen to wildtype control levels. Taken together, these data provide direct evidence for the respective beneficial effects of exercise training and carvedilol in α 2A /α 2C ArKO mice preventing cardiac dysfunction. The different mechanisms associated with beneficial effects of exercise training and carvedilol suggest future studies associating both therapies.

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Impact of 6 months of therapy with carvedilol on muscle sympathetic nerve activity in heart failure patients

Cited by 52 publications

References 29 publications

Restoration of Pulsatile Flow Reduces Sympathetic Nerve Activity Among Individuals With Continuous-Flow Left Ventricular Assist Devices

Restoration of Pulsatile Flow Reduces Sympathetic Nerve Activity Among Individuals With Continuous-Flow Left Ventricular Assist Devices

The preserved autonomic functions may provide the asymptomatic clinical status in heart failure despite advanced left ventricular systolic dysfunction

Effect of exercise training and carvedilol treatment on cardiac function and structure in mice with sympathetic hyperactivity-induced heart failure

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