Aerobic Training Decreases B-Type Natriuretic Peptide Expression and Adrenergic Activation in Patients With Heart Failure
Claudio Passino, Silvia Severino, Roberta Poletti, Massimo F. Piepoli, Chiara ...Mammini, Aldo Clerico, Alessandra Gabutti, Guido Nassi, Michele Emdin
To evaluate the effect of physical training on neurohormonal activation in subjects with chronic heart failure, 95 patients were randomized into group T (training) and group C (no training). Neurohormonal assays, quality-of-life (QOL) questionnaire, echocardiogram, and cardiopulmonary stress test were performed in all patients. At the ninth month, trained patients showed improvement of workload, peak oxygen uptake, systolic function, and QOL. B-type natriuretic peptide and norepinephrine plasma values decreased after training, with no changes in group C. Physical training benefit on functional capacity and QOL in patients with heart failure is associated with an improvement in neurohormonal imbalance.
We sought to evaluate the effect of physical training on neurohormonal activation in patients with heart failure (HF).
Patients with HF benefit from physical training. Chronic neurohormonal activation has detrimental effects on ventricular remodeling and prognosis of patients with HF.
A total of 95 patients with HF were assigned randomly into two groups: 47 patients (group T) underwent a nine-month training program at 60% of the maximal oxygen uptake (Vo2), whereas 48 patients did not (group C). The exercise load was adjusted during follow-up to achieve a progressive training effect. Plasma assay of B-type natriuretic peptide (BNP), amino-terminal pro-brain natriuretic peptide (NT-proBNP), norepinephrine, plasma renin activity, and aldosterone; quality-of-life questionnaire; echocardiogram; and cardiopulmonary stress test were performed upon enrollment and at the third and ninth month.
A total of 85 patients completed the protocol (44 in group T, left ventricular ejection fraction EF 35 ± 2%, mean ± SEM; and 41 in group C, EF 32 ± 2%, p = NS). At the ninth month, patients who underwent training showed an improvement in workload (+14%, p < 0.001), peak Vo2(+13%, p < 0.001), systolic function (EF +9%, p < 0.01), and quality of life. We noted that BNP, NT-proBNP, and norepinephrine values decreased after training (−34%, p < 0.01; −32%, p < 0.05; −26%, p < 0.01, respectively). Increase in peak Vo2with training correlated significantly with the decrease in both BNP/NT-proBNP level (p < 0.001 and p < 0.01, respectively). Patients who did not undergo training showed no changes.
Clinical benefits after physical training in patients with HF are associated with blunting of adrenergic overactivity and of natriuretic peptide overexpression.
This study sought to investigate sex-related differences in reverse remodeling (RR).
RR, that is, the recovery from left ventricular (LV) dilation and dysfunction in response to treatment for heart ...failure (HF), is associated with improved prognosis.
Data from patients with stable systolic HF (LV ejection fraction LVEF of <50%) undergoing 2 transthoracic echocardiograms within 12 ± 2 months were analyzed. Reverse remodeling was defined as a ≥15% reduction in LV end-systolic volume index.
A total of 927 patients were evaluated (68 ± 12 years; median LVEF = 35% interquartile range: 30% to 43%; 27% women). Ischemic HF was less often encountered in women (33% vs. 60%, respectively; p < 0.001), whereas most characteristics did not differ with regard to sex. Women showed a higher incidence of RR (41% vs. 27%, respectively; p < 0.001), despite similar baseline LV volume and function. RR was more frequent among women in the subgroups with either ischemic or nonischemic HF, as well as in all categories of systolic dysfunction (LVEF ≤35% or >35%, according to current indication for device implantation, and LVEF <40% or 40% to 50% according to the definition of HF with reduced or mid-range EF). In the whole population, female sex was an independent predictor of RR (hazard ratio: 1.54; 95% confidence interval: 1.11 to 2.14; p = 0.011), together with cause of HF, disease duration, and left bundle branch block. Female sex was again an independent predictor of RR in all LVEF categories.
Reverse remodeling is more frequent among women, regardless of cause and severity of LV dysfunction. Female sex is an independent predictor of RR in all categories of LV systolic dysfunction.
Display omitted
R2 was defined according to three different criteria, all present within literature: 1) >15% decrease in left ventricular end-systolic volume index (LVESVi) (criterion 1); 2) increase in LV ejection ...fraction, LVEF, >10U with a >10% decrease in LV end-diastolic volume index (LVEDVi) (criterion 2); 3) an increase in LVEF >10U or a >10% decrease in LVEDVi (criterion 3).
Abstract only
Purpose:
Cheyne Stokes respiration, that is periodic apnea/hyperpnea of central origin (CSR), has been separately described both during night (nCSR) and daytime (dCSR) in HF and ...associated with worse prognosis. The relationships between severity of nCSR and of dCSR have not yet been established.
Methods:
we enrolled 439 consecutive HF patients (aged 65±13 years, 76% males; NYHA class III-IV 33%, LVEF: 32±9%, mean±SD) on current guideline-directed therapy (96% betablockers, 94% ACE-inhibitors/angiotensin receptor blockers, 22% CRT). All patients underwent a 24hour cardiorespiratory polygraphic recording (nasal flow plus chest and abdomen respirograms) for detection of hypo/apnea phenomenon, clinical and neurohormonal evaluation, cardiopulmonary exercise testing, echocardiography and Holter monitoring.
Results:
four groups were identified according to severity of nCSR (AHI <5, 17%; mild, 5 to 15, 24%; moderate, 15 to 30, 30%; severe, >30, 29%) and dCSR (normal, apnea/hypopnea index, AHI <5, 38%; mild, 5 to 15, 32%; moderate, 15 to 30, 29%; severe, >30, 9%); nocturnal obstructive apnea prevalence (AHI >5) was 10% (1% daytime). Notably, in patients with significant (AHI>15) nCSR, dCSR had the highest prevalence (daytime AHI>15, 71%, daytime AHI>30, 26%). Both severe dCSR and nCSR were associated (p<0.01) with age, male gender, NYHA class III-IV, nonsustained ventricular tachycardia at Holter monitoring, higher plasma NT-proBNP and norepinephrine, lower pVO2, ventilatory inefficiency as assessed by the slope of ventilation to carbon dioxide production, LV dilatation (assessed by end-systolic and diastolic diameters) and hypertrophy (assessed by LV indexed mass), right ventricular dimension. Severe dCSR, but not nCSR, was associated with lower LVEF, increased prevalence of atrial fibrillation and diabetes.
Conclusions:
significant dCSR is prevalent in HF, namely in patients with more severe nCSR (AHI>15). Both dCSR and nCSR are associated with neurohormonal activation, greater left and right ventricular volumes, increased ventricular arrhythmic burden and lower functional capacity, while lower LVEF as well atrial fibrillation are associated with dCSR only. Risk stratification and therapeutic strategies should consider dCSR.
Ventilatory impairment is known to occur in patients with heart failure (HF). Alveolar volume (VA) is measured by the dilution of an inert gas during a single breath-hold maneuver. Such measurement ...is sensitive to ventilatory disturbances. We conducted a prospective, observational study to establish the prognostic value of VA in systolic HF.
We studied 260 consecutive patients who were hospitalized for systolic HF. All patients were evaluated under stable clinical conditions, before hospital discharge. Lung function studies included spirometry and determination of the lung diffusing capacity for carbon monoxide (DLCO) by the single-breath method. We also measured the cardiothoracic ratio on frontal chest radiographs, and the circulating levels of N-terminal pro-hormone of B-type natriuretic peptide (NT-proBNP). The hazard ratio (HR) of death was estimated with Cox regression, and the percentiles of survival time with Laplace regression. For survival analysis, VA was categorized as < 80% (n = 135), or ≥ 80% of the predicted value (n = 125).
Follow-up had a median duration of 2.7 years (interquartile range, 1.1 to 4.2 years). The crude mortality rate was 27% in the whole sample, 36% in patients with VA < 80%, and 16% in those with VA ≥ 80%. The HR of death was 2.3-fold higher in patients with VA < 80% than in those with VA ≥80% (p = 0.002). After adjusting for age, New York Heart Association class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO, COPD comorbidity, use of beta-blockers and angiotensin converting enzyme inhibitors, the HR decreased to 1.9 but remained statistically significant (p = 0.039). Two percent of the patients with VA < 80% died about 0.9 years earlier than those with VA ≥ 80% (p = 0.033). The difference in survival time at the 20th percentile was 0.8 years.
VA is a significant, independent predictor of reduced survival in patients with systolic HF.
Several biomarkers have been tested for screening, diagnosis and prognosis purposes, as well as to guide treatment in heart failure, but only the assay of circulating B-type natriuretic peptides has ...widely recognized applications for clinical decision-making. Natriuretic peptides are sensitive in detecting the clinically overt or subclinical myocardial damage, but their plasma levels are increased following every generic insult to the cardiovascular system. Novel biomarkers are required to identify specific pathways of disease progression, such as diverse neurohormonal axes activation, inflammation and fibrogenesis, and to act as a tool for therapeutic tailoring. In this view, Gal-3 and ST-2 assays seem very promising, given their involvement in mechanisms of cardiac fibrosis and their prognostic value.
We aimed to evaluate the impact of glycometabolic imbalance as assessed by glycosylated haemoglobin HbA(1c) on neurohormonal activation and outcome in chronic heart failure (CHF).
Nine hundred and ...twenty CHF patients (65 ± 12 years, left ventricular ejection fraction 33 ± 10%, 29% diabetic patients) underwent a thorough humoral and clinical characterization, including HbA(1c), and were then followed up for the endpoint of cardiac death. In the whole population, diagnosis of diabetes resulted in no difference in neurohormonal or echocardiographic data, or in outcome. Conversely, the diabetic patients with HbA(1c) above 7% showed, in comparison to both diabetic patients with HbA(1c) below 7% and non-diabetic individuals, higher plasma renin activity (1.81, 0.48-5.68 vs. 1.23, 0.43-2.8 and 1.29, 0.44-5 ng/ml/h, respectively; P < 0.01 for both), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (1602, 826-3498 vs. 1022, 500-3543 and 1134, 455-3545 ng/l, respectively; P < 0.01 for both) and worse symptoms with a higher rate of cardiac mortality vs. both diabetic patients with HbA1(c) below 7% and non-diabetic individuals (P < 0.05 for both). In the left ventricular ejection fraction 38-50% tertile (mild left ventricular dysfunction), elevated HbA(1c) was associated with higher NT-pro-BNP and PRA (P < 0.01), and, alongside NT-pro-BNP, resulted the only independent predictor of outcome beyond diagnosis of diabetes. HbA(1c) failed to show up differences in neuroendocrine activation or in outcome in moderate and severe left ventricular dysfunction tertiles.
Glycometabolic imbalance, as represented by HbA(1c), is associated with neurohormonal activation and poor prognosis in CHF patients, beyond diabetes. The impact of metabolic derangement on prognosis appears greater at the early stages of CHF, when it might exacerbate neurohormonal activation.
Abstract
Background:
Heart failure (HF) is characterised by reduced tolerance to effort, associated with progressive fatigue and dyspnoea. Neuro-hormonal activation is a hallmark of HF and influences ...its clinical evolution.
Aim:
To evaluate the relationship between neuro-hormonal activation, exercise capacity and ventilatory efficiency.
Methods and results:
154 HF patients (127 males, 62±1 years) underwent cardiopulmonary exercise testing and resting blood sampling for assay of plasma brain natriuretic peptide (BNP), NT-proBNP, norepinephrine, epinephrine, aldosterone and plasma renin activity (PRA). BNP and NT-proBNP levels correlated with peak oxygen consumption (VO2) (both R=−0.53, p<0.001), VE/VCO2 slope (R=0.56; p<0.001 and R=0.58; p<0.001, respectively) and maximum workload (R=−0.49; p<0.001 and R=−0.47; p<0.001, respectively). Norepinephrine correlated slightly less with peak VO2 (R=−0.38, p<0.001), VE/VCO2 (R=0.45; p<0.001) and maximum workload (R=−0.35; p<0.001). There was a significant inverse correlation between left ventricular ejection fraction and BNP (R=−0.48, p<0.001), NT-proBNP (R=−0.42; p<0.001) and norepinephrine (R=−0.43; p<0.001). Weaker correlations were found for PRA, exercise parameters and ejection fraction. ROC curves showed that BNP was able to identify patients with peak VO2<14 ml/min/kg (cut-off 98 pg/ml, AUC 0.775) and a VE/VCO2>35 (cut-off 183 pg/ml, AUC 0.797), as well as NT-proBNP (cut-off 537 pg/ml, AUC 0.799 and cut-off 1010 pg/ml, AUC 0.768, respectively) and norepinephrine (cut-off 454 pg/ml, AUC 0.716 and cut-off 575 pg/ml, AUC 0.783, respectively).
Conclusion:
Haemodynamic impairment (as indicated by BNP and NT-proBNP plasma values) and sympathetic activation predict exercise capacity and ventilatory efficiency in HF patients.
There is evidence that natriuretic peptide (namely atrial and/or B-type natriuretic peptides) plasma concentration may be elevated in many clinical conditions besides cardiovascular diseases, the ...most frequent being lung diseases, renal and liver failure, acute cerebrovascular events, acute and chronic inflammatory diseases and certain metabolic and endocrine disorders. In general, increased circulating levels of natriuretic peptides (compared to the normal range of a healthy population) may be considered expression of activation of the neuro-endocrine system, which can be the cause or consequence of cardiac stressor events. Furthermore, some variables, such as gender and obesity, may affect natriuretic peptide secretion and plasma concentration by completely extra-cardiac mechanisms. Increased expression of the natriuretic peptide system, counteracting neuro-hormonal and immunological activation, may occur in many clinical conditions, as witnessed by the considerable number of diseases in which the natriuretic peptide system has been found to be altered. Several studies have demonstrated that higher circulating levels of natriuretic peptides represent a strong independent risk factor for major cardiovascular complications and/or death, even in extra-cardiac diseases. Because several of these diseases may be present in patients with left ventricular dysfunction, the possible influence on diagnostic and prognostic accuracy of natriuretic peptides in heart failure will be discussed. Clin Chem Lab Med 2008;46:1515–23.
PDF
