Heart failure and sleep-disordered breathing: susceptibility to reduced muscle strength and preclinical congestion (SICA-HF cohort).

AIMS: Increased sympathetic activation in patients with heart failure (HF) and sleep-disordered breathing (SDB) provokes cardiac decompensation and protein degradation and could lead to muscle wasting and muscle weakness. The aim of this study was to investigate the differences in body composition, muscle function, and the susceptibility of preclinical congestion among patients with HF and SDB compared with those without SDB. METHODS AND RESULTS: We studied 111 outpatients with stable HF who were enrolled into the Studies Investigating Co-morbidities Aggravating Heart Failure. Echocardiography, short physical performance battery (SPPB), cardiopulmonary exercise testing, dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), tests of muscle strength, and polygraphy were performed. SDB was defined as apnoea/hypopnoea index (AHI) >5 per hour of sleep. Central sleep apnoea (CSA) and obstructive sleep apnoea (OSA) were defined as AHI >50% of central or obstructive origin, respectively. A total of 74 patients (66.7%) had any form of SDB [CSA (24 patients, 32.4%), OSA (47 patients, 63.5%)]. Patients with SDB showed increased muscle weakness (chair stand), reduced muscle strength, and lower values of SPPB score (P < 0.05). Patients with SDB did not show overt clinical signs of cardiac decompensation compared with those without SDB (P > 0.05) but had increased amounts of water (total body water, intracellular, and extracellular) measured using BIA (P < 0.05). Increased amounts of total body water were associated with the severity of SDB and inversely with muscle strength and exercise capacity measured by anaerobic threshold (P < 0.05). Altogether, 17 patients had muscle wasting. Of these, 11 (65%) patients had SDB (statistically not significant). CONCLUSIONS: SDB is highly prevalent in patients with HF. Patients with SDB have lower muscle strength and tend to be more susceptible to preclinical congestion.

Pupil dilation as an implicit measure of appetitive Pavlovian learning.

Appetitive Pavlovian conditioning is a learning mechanism of fundamental biological and pathophysiological significance. Nonetheless, its exploration in humans remains sparse, which is partly attributed to the lack of an established psychophysiological parameter that aptly represents conditioned responding. This study evaluated pupil diameter and other ocular response measures (gaze dwelling time, blink duration and count) as indices of conditioning. Additionally, a learning model was used to infer participants' learning progress on the basis of their pupil dilation. Twenty-nine healthy volunteers completed an appetitive differential delay conditioning paradigm with a primary reward, while the ocular response measures along with other psychophysiological (heart rate, electrodermal activity, postauricular and eyeblink reflex) and behavioral (ratings, contingency awareness) parameters were obtained to examine the relation among different measures. A significantly stronger increase in pupil diameter, longer gaze duration and shorter eyeblink duration was observed in response to the reward-predicting cue compared to the control cue. The Pearce-Hall attention model best predicted the trial-by-trial pupil diameter. This conditioned response was corroborated by a pronounced heart rate deceleration to the reward-predicting cue, while no conditioning effect was observed in the electrodermal activity or startle responses. There was no discernible correlation between the psychophysiological response measures. These results highlight the potential value of ocular response measures as sensitive indices for representing appetitive conditioning.

Opposing roles for amygdala and vmPFC in the return of appetitive conditioned responses in humans.

Learning accounts of addiction and obesity emphasize the persistent power of Pavlovian reward cues to trigger craving and increase relapse risk. While extinction can reduce conditioned responding, Pavlovian relapse phenomena-the return of conditioned responding following successful extinction-challenge the long-term success of extinction-based treatments. Translational laboratory models of Pavlovian relapse could therefore represent a valuable tool to investigate the mechanisms mediating relapse, although so far human research has mostly focused on return of fear phenomena. To this end we developed an appetitive conditioning paradigm with liquid food rewards in combination with a 3-day design to investigate the return of appetitive Pavlovian responses and the involved neural structures in healthy subjects. Pavlovian conditioning (day 1) was assessed in 62 participants, and a subsample (n = 33) further completed extinction (day 2) and a reinstatement test (day 3). Conditioned responding was assessed on explicit (pleasantness ratings) and implicit measures (reaction time, skin conductance, heart rate, startle response) and reinstatement effects were further evaluated using fMRI. We observed a return of conditioned responding during the reinstatement test, evident by enhanced skin conductance responses, accompanied by enhanced BOLD responses in the amygdala. On an individual level, psychophysiological reinstatement intensity was significantly anticorrelated with ventromedial prefrontal cortex (vmPFC) activation, and marginally anticorrelated with enhanced amygdala-vmPFC connectivity during late reinstatement. Our results extend evidence from return of fear phenomena to the appetitive domain, and highlight the role of the vmPFC and its functional connection with the amygdala in regulating appetitive Pavlovian relapse.

Body weight changes and incidence of cachexia after stroke.

BACKGROUND: Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single-centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome. METHODS: Sixty-seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m2 , 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0-12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow-up. Body composition was examined by dual energy X-ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m2 ) was ≤5.45 kg/m2 for female patient and ≤7.25 kg/m2 for male patient. RESULTS: According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non-cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P < 0.05), Barthel Index was 22% lower (71 ± 39, P < 0.01), and handgrip strength was 34% lower (21.9 ± 13.0, P < 0.05) in cachectic compared to non-cachectic patients after 12 months. The low physical performance if defined by Barthel Index <60 points was linked to the lean tissue wasting (OR 44.8, P < 0.01), presence of cachexia (OR 20.8, P < 0.01), and low body mass index <25 kg/m2 (OR 11.5, P < 0.05). After adjustment for cofounders, lean tissue wasting remained independently associated with the low physical performance at 12 months follow-up (OR 137.9, P < 0.05). CONCLUSIONS: In this cohort study, every fifth patient with ischemic stroke fulfilled the criteria of cachexia within 12 months after index event. The incidence of cachexia was 21%. Cachectic patients showed the lowest functional and physical capacity.

Sleep-disordered breathing in heart failure: facts and numbers.

Sleep-disordered breathing has a high prevalence in the general population, but is especially prominent in patients with heart failure (HF). HF and sleep-disordered breathing share a bidirectional relationship, with sleep-disordered breathing being both cause and effect of poor cardiac functioning. The high inter-individual variability of symptom presentation can impede the clinical diagnostic process. Polysomnography is the gold-standard method of diagnosing sleep-disordered breathing. Therapy of sleep-disordered breathing should always consist of optimizing the treatment of the underlying disorder of HF. Additional therapeutic measures include continuous positive airway pressure ventilation therapy. New therapeutic options using neurostimulation are yielding promising results; however, long-term benefits still need to be confirmed.