Abnormal adrenergic activation is the major determinant of reduced functional capacity in heart failure with preserved ejection fraction

Messias, Leandro Rocha; Messias, Ana; Miranda, Sandra Marina Ribeiro de; Wiefels, Christiane; Ferreira, A.; Santos, L.M.; Teixeira, José Antônio Caldas; Maróstica, Elisabeth; Mesquita, Cláudio Tinoco

doi:10.1016/j.ijcard.2015.10.224

Cited by 10 publications

(3 citation statements)

References 9 publications

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“…As expected, estimates of HFpEF prevalence were higher in samples of outpatients and in one study with primary care patients. 7,10,11,[20][21][22][23] Sex distribution of Brazilian patients with HFpEF corroborates data from international studies, with higher proportion of women. 18 We could not detect a clear pattern in terms of age rages or mean age, which were similar between HFpEF patients and mixed HF patients.…”

Section: Discussionsupporting

confidence: 74%

Heart Failure with Preserved Ejection Fraction in Brazil: A Systematic Review

Bocchi,

Brandão,

Mesquita

et al. 2023

ABC Heart Fail Cardiomyop

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Heart failure with preserved ejection fraction (HFpEF) is the most common condition of heart failure (HF) in patients over 65 years of age and is associated with high morbidity and mortality. Epidemiological data on this condition are still scarce in Brazil and these data are relevant for a better understanding of the impact and unmet needs in HFpEF and for the planning of actions to improve prevention, diagnosis, and treatment of this disease.The objective of the study was to identify evidence on the epidemiology and clinical characteristics of Brazilian patients with HFpEF.We systematically reviewed observational and clinical studies evaluating epidemiological and clinical data of Brazilian patients with HFpEF in the Pubmed/MEDLINE and LILACS databases, following PRISMA guidelines.The prevalence of HFpEF in patients with confirmed HF ranged from 28.2 to 59.0% in the outpatient setting and from 20.0% to 53.1% in the hospital setting. Among patients with suspected HF, the prevalence of patients with LVEF>50% ranged from 29.0 to 37.6%. The most frequently reported comorbidities were systemic arterial hypertension and diabetes, with a prevalence of 57.4 to 100.0% in studies involving only patients with HFpEF, and from 10.2 to 49.1% in studies on patients with HF with normal ejection fraction (n = 14). Data on mortality and hospitalization rates were scarce.Despite few and heterogeneous data on the prevalence of HFpEF in Brazil, the prevalence of this condition in primary care patients and in hospitalized patients was relatively high.

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Section: Discussionsupporting

confidence: 74%

Heart Failure with Preserved Ejection Fraction in Brazil: A Systematic Review

Bocchi,

Brandão,

Mesquita

et al. 2023

ABC Heart Fail Cardiomyop

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“…Indeed, bradyarrhythmias account for up to half of the deaths in HF (Luu et al, 1989;Stevenson et al, 1993;Uretsky and Sheahan, 1997;Faggiano et al, 2001;Packer et al, 2009;Bloch Thomsen et al, 2010;Gang et al, 2010;Glukhov et al, 2013;Lou et al, 2014). Moreover, in association with autonomic dysfunction (Colucci et al, 1989;Bristow et al, 1990;Samejima et al, 2003;Messias et al, 2016), slowing of the intrinsic HR by SAN remodeling might limit HR modulation to exercise (Sanders et al, 2004), the chronotropic incompetence observed during the HF process (Weber et al, 1982;Higginbotham et al, 1983;Brubaker et al, 2006;Brubaker and Kitzman, 2011;Benes et al, 2013).…”

Section: Ryr2 and Sinus Node Dysfunctionmentioning

confidence: 99%

RyR2 and Calcium Release in Heart Failure

et al. 2021

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Heart Failure (HF) is defined as the inability of the heart to efficiently pump out enough blood to maintain the body's needs, first at exercise and then also at rest. Alterations in Ca2+ handling contributes to the diminished contraction and relaxation of the failing heart. While most Ca2+ handling protein expression and/or function has been shown to be altered in many models of experimental HF, in this review, we focus in the sarcoplasmic reticulum (SR) Ca2+ release channel, the type 2 ryanodine receptor (RyR2). Various modifications of this channel inducing alterations in its function have been reported. The first was the fact that RyR2 is less responsive to activation by Ca2+ entry through the L-Type calcium channel, which is the functional result of an ultrastructural remodeling of the ventricular cardiomyocyte, with fewer and disorganized transverse (T) tubules. HF is associated with an elevated sympathetic tone and in an oxidant environment. In this line, enhanced RyR2 phosphorylation and oxidation have been shown in human and experimental HF. After several controversies, it is now generally accepted that phosphorylation of RyR2 at the Calmodulin Kinase II site (S2814) is involved in both the depressed contractile function and the enhanced arrhythmic susceptibility of the failing heart. Diminished expression of the FK506 binding protein, FKBP12.6, may also contribute. While these alterations have been mostly studied in the left ventricle of HF with reduced ejection fraction, recent studies are looking at HF with preserved ejection fraction. Moreover, alterations in the RyR2 in HF may also contribute to supraventricular defects associated with HF such as sinus node dysfunction and atrial fibrillation.

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“…In this way, chronotropic incompetence, defined as the inability of the heart to increase adequately during physical exertion, has been proposed as one of the key mechanisms linked to exercise intolerance in HFpEF in some studies. [8][9][10]19 The pathophysiology of impaired HR response is complex and has been associated to autonomic imbalances such as (a) the decrease in betareceptor density; 23 (b) the desensitization of beta-receptors despite the presence of increased circulating catecholamine levels; [24][25][26] and (c) the remodelling of sinus node function. 27 However, the causative role of chronotropic incompetence in the pathophysiology of this syndrome is difficult to establish.…”

Section: Prevalence and Pathophysiology Of Chronotropic Incompetencementioning

confidence: 99%

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction

et al. 2018

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AimsThe mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF.Methods and resultsWe prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO2). The mean (standard deviation) peak VO2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta‐HR (HR at peak exercise − HR at rest), chronotropic index (CI) = (HR at peak exercise − resting HR)/[(220 − age) − resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise − HR at rest)/[119 + (HR at rest/2) − (age/2) − 5 − HR at rest]. In a bivariate setting, peak VO2 was positively and significantly correlated with Delta‐HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO2. We found a linear relationship between Delta‐HR and peak VO2 (β coefficient of 0.03; 95% confidence interval: 0.004–0.05; P = 0.030); conversely, the association among CIs and peak VO2 was exponentially shaped.ConclusionsIn patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity.

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Abnormal adrenergic activation is the major determinant of reduced functional capacity in heart failure with preserved ejection fraction

Cited by 10 publications

References 9 publications

Heart Failure with Preserved Ejection Fraction in Brazil: A Systematic Review

Heart Failure with Preserved Ejection Fraction in Brazil: A Systematic Review

RyR2 and Calcium Release in Heart Failure

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction

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