Resetting the neurohormonal balance in heart failure (HF). the relevance of the natriuretic peptide (NP) system to the clinical management of patients with HF

The natriuretic peptide (NP) system, which includes atrial natriuretic peptide, B-type natriuretic peptide, and C-type natriuretic peptide, has an important role in cardiovascular homeostasis, promoting a number of physiological effects including diuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system. Heart failure (HF) is associated with defects in NP processing and synthesis, and there is a strong relationship between NP levels and disease state. NPs are useful biomarkers in HF, and their use in diagnosis and evaluation of prognosis is well established, particularly in patients with HF with reduced ejection fraction (HFrEF). There has also been interest in their use to guide disease management and therapeutic decision making. An understanding of NPs in HF has also resulted in interest in synthetic NPs for the treatment of HF and in treatments that target neprilysin, a protease that degrades NPs. A novel drug, the angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696), which simultaneously inhibits neprilysin and blocks the angiotensin II type I receptor, was shown to have a favorable efficacy and safety profile in patients with HFrEF and has been approved for use in such patients in Europe and the USA. In light of the development of treatments that target neprilysin and of recent data in relation to synthetic NPs, it is timely to review the current understanding of the role of NPs in HF and their use in diagnosis, evaluating prognosis and guiding treatment, as well as their place in HF therapy

Physical activity guidelines and cardiovascular risk in children: a cross-sectional analysis to determine whether 60 minutes is enough

Background Physical activity reduces cardiovascular mortality and morbidity. The World Health Organisation (WHO) recommends children engage in 60 min daily moderate-to-vigorous physical activity (MVPA). The effect of compliance with this recommendation on childhood cardiovascular risk has not been empirically tested. To evaluate whether achieving recommendations results in reduced composite-cardiovascular risk score (CCVR) in children, and to examine if vigorous PA (VPA) has independent risk-reduction effects. Methods PA was measured using accelerometry in 182 children (9–11 years). Subjects were grouped according to achievement of 60 min daily MVPA (active) or not (inactive). CCVR was calculated (sum of z-scores: DXA body fat %, blood pressure, VO2peak, flow mediated dilation, left ventricular diastolic function; CVR score ≥1SD indicated ‘higher risk’). The cohort was further split into quintiles for VPA and odds ratios (OR) calculated for each quintile. Results Active children (92 (53 boys)) undertook more MVPA (38 ± 11 min, P  0.05). CCVR in the lowest VPA quintile was significantly greater than the highest quintile (3.9 ± 0.6, P < 0.05), and the OR was 4.7 times higher. Conclusion Achievement of current guidelines has positive effects on body composition and cardiorespiratory fitness, but not CCVR. Vigorous physical activity appears to have beneficial effects on CVD risk, independent of moderate PA, implying a more prescriptive approach may be needed for future VPA guidelines

Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation

Background: In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods: We performed a post hoc analysis of the BIOSTAT-CHF study. We evaluated 1548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure hospitalisation stratified by heart rhythm and heart rate at baseline. Results: Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at 9 months was associated with reduced incidence of the primary outcome in both SR and AF patients [HR per 10 bpm decrease—SR: 0.83 (0.75–0.91), p &lt; 0.001; AF: 0.89 (0.81–0.98), p = 0.018], whereas the relationship was less strong for achieved heart rate in AF [HR per 10 bpm higher—SR: 1.26 (1.10–1.46), p = 0.001; AF: 1.08 (0.94–1.23), p = 0.18]. Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions: Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate

Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate-intensity cycle exercise

New Findings What is the central question of this study? We explored whether heart failure (HF) patients demonstrate different exercise-induced brachial artery shear rate patterns compared with control subjects. What is the main finding and its importance? Moderate-intensity cycle exercise in HF patients is associated with an attenuated increase in brachial artery anterograde and mean shear rate and skin temperature. Differences between HF patients and control subjects cannot be explained fully by differences in workload. HF patients demonstrate a less favourable shear rate pattern during cycle exercise compared with control subjects. Repeated elevations in shear rate (SR) in conduit arteries, which occur during exercise, represent a key stimulus to improve vascular function. We explored whether heart failure (HF) patients demonstrate distinct changes in SR in response to moderate-intensity cycle exercise compared with healthy control subjects. We examined brachial artery SR during 40 min of cycle exercise at a work rate equivalent to 65% peak oxygen uptake in 14 HF patients (65 ± 7 years old, 13 men and one woman) and 14 control subjects (61 ± 5 years old, 12 men and two women). Brachial artery diameter, SR and oscillatory shear index (OSI) were assessed using ultrasound at baseline and during exercise. The HF patients demonstrated an attenuated increase in mean and anterograde brachial artery SR during exercise compared with control subjects (time × group interaction, P = 0.003 and P 0.05). In conclusion, HF patients demonstrate a less favourable SR pattern during cycle exercise than control subjects, characterized by an attenuated mean and anterograde SR and by increased OSI

Worry is associated with robust reductions in heart rate variability: a transdiagnostic study of anxiety psychopathology

Background Individuals with anxiety disorders display reduced resting-state heart rate variability (HRV), although findings have been contradictory and the role of specific symptoms has been less clear. It is possible that HRV reductions may transcend diagnostic categories, consistent with dimensional-trait models of psychopathology. Here we investigated whether anxiety disorders or symptoms of anxiety, stress, worry and depression are more strongly associated with resting-state HRV. Methods Resting-state HRV was calculated in participants with clinical anxiety (n = 25) and healthy controls (n = 58). Symptom severity measures of worry, anxiety, stress, and depression were also collected from participants, regardless of diagnosis. Results Participants who fulfilled DSM-IV criteria for an anxiety disorder displayed diminished HRV, a difference at trend level significance (p = .1, Hedges’ g = -.37, BF10 = .84). High worriers (Total n = 41; n = 22 diagnosed with an anxiety disorder and n = 19 not meeting criteria for any psychopathology) displayed a robust reduction in resting state HRV relative to low worriers (p = .001, Hedges’ g = -.75, BF10 = 28.16). Conclusions The specific symptom of worry – not the diagnosis of an anxiety disorder – was associated with the most robust reductions in HRV, indicating that HRV may provide a transdiagnostic biomarker of worry. These results enhance understanding of the relationship between the cardiac autonomic nervous system and anxiety psychopathology, providing support for dimensional-trait models consistent with the Research Domain Criteria framework

Left Atrium in Heart Failure With Preserved Ejection Fraction

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Cognitive Impairment in Heart Failure

Cognitive impairment (CI) is increasingly recognized as a common adverse consequence of heart failure (HF). Although the exact mechanisms remain unclear, microembolism, chronic or intermittent cerebral hypoperfusion, and/or impaired cerebral vessel reactivity that lead to cerebral hypoxia and ischemic brain damage seem to underlie the development of CI in HF. Cognitive decline in HF is characterized by deficits in one or more cognition domains, including attention, memory, executive function, and psychomotor speed. These deficits may affect patients' decision-making capacity and interfere with their ability to comply with treatment requirements, recognize and self-manage disease worsening symptoms. CI may have fluctuations in severity over time, improve with effective HF treatment or progress to dementia. CI is independently associated with disability, mortality, and decreased quality of life of HF patients. It is essential therefore for health professionals in their routine evaluations of HF patients to become familiar with assessment of cognitive performance using standardized screening instruments. Future studies should focus on elucidating the mechanisms that underlie CI in HF and establishing preventive strategies and treatment approaches

Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.