Phenotyping congestion in patients with acutely decompensated heart failure with preserved and reduced ejection fraction: The Decongestion duRing therapY for acute decOmpensated heart failure in HFpEF vs HFrEF- DRY-OFF study.

AIMS: To evaluate pulmonary and intravascular congestion at admission and repeatedly during hospitalization for acute decompensated heart failure (ADHF) in HFrEF and HFpEF patients using lung (LUS) and inferior vena cava (IVC) ultrasound. METHODS AND RESULTS: Three-hundred-fourteen patients (82±9 years; HFpEF =172; HFrEF=142) admitted to Internal Medicine wards for ADHF were enrolled in a multi-center prospective study. At admission HFrEF presented higher indexes of pulmonary and intravascular congestion (LUS-score: 0.9 ±â€¯0.4 vs 0.7 ±â€¯0.4; p<0.01; IVC end-expiratory diameter: 21.6 ±â€¯5.1 mm vs 20±5.5 mm, p<0.01; IVC collapsibility index 24.4 ±â€¯17.4% vs 30.9 ±â€¯21.1% p<0.01) and higher Nt-proBNP values (8010 vs 3900 ng/l; p<0.001). At discharge, HFrEF still presented higher B-scores (0.4 ±â€¯4 vs 0.3 ±â€¯0.4; p = 0.023), while intravascular congestion improved to a greater extent, thus IVC measurements were similar in the two groups. No differences in diuretic doses, urine output, hemoconcentration, worsening renal function were found. At 90-days follow up HF readmission/death did not differ in HFpEF and HFrEF (28% vs 31%, p = 0,48). Residual congestion was associated with HF readmission/death considering the whole population; while intravascular congestion predicted readmission/death in the HFrEF, no association between sonographic indexes and the outcome was found in HFpEF. CONCLUSIONS: Serial assessment of pulmonary and intravascular congestion revealed a higher burden of fluid overload in HFrEF and, conversely, a greater reduction in intravascular venous congestion with diuretic treatment. Although other factors beyond EF could play a role in congestion/decongestion patterns, our data may be relevant for further phenotyping HF patients, considering the importance of decongestion optimization in the clinical approach.

Effects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study.

BACKGROUND: Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. METHODS: Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24-51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. RESULTS: BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). CONCLUSION: BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

Glioblastoma del nervio óptico detectado por PET/TC cerebral con 11C-Metionina / Optic nerve glioblastoma detected by 11C-Methionine brain PET/CT

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Complement and contact system activation in acute congestive heart failure patients.

Recent experimental data indicate a pathogenic role of complement activation in congestive heart failure (CHF). The aim of this study was to evaluate contact and complement systems activation in patients hospitalized for an acute episode of CHF. Forty-two of 80 consecutive patients admitted at our hospital with confirmed diagnosis of acute CHF were enrolled. They underwent blood sampling within 24 h from admission (T0) and at clinical stability (T1). Patients were stratified for ejection fraction (EF) based on echocardiographic test. We measured plasma levels of C3, C4, sC5b-9 and cleaved high molecular weight kininogen (contact activation marker). At T1, C3 levels increased significantly compared to T0 (97 ± 2 versus 104 ± 3% of total pooled plasma, P < 0·01). Classifying patients according to EF, only patients with preserved EF presented a significant increase of C3 from T0 to T1 (99 ± 3 versus 108 ± 4%, P = 0·03). When the sample was stratified according to clinical outcome, C3 (98 ± 3 versus 104 ± 4%, P = 0·03) and sC5b-9 levels (204 ± 10 versus 230 ± 11 ng/ml, P = 0·03) were increased in patients who had positive outcome after hospitalization. CHF patients with preserved EF and positive outcome after hospitalization showed higher levels of sC5b-9 in the T1 period compared with T0 (211 ± 14 versus 243 ± 14 ng/ml, P = 0·04). Our results suggest that the complement system reacts differently if CHF occurs with preserved or reduced EF. This finding is interesting if we consider the difference in epidemiology, pathogenesis and possible therapeutic approaches of these two clinical entities.

Post-resistance exercise hemodynamic and autonomic responses: Comparison between normotensive and hypertensive men.

To compare post-resistance exercise hypotension (PREH) and its mechanisms in normotensive and hypertensive individuals, 14 normotensives and 12 hypertensives underwent two experimental sessions: control (rest) and exercise (seven exercises, three sets, 50% of one repetition maximum). Hemodynamic and autonomic clinic measurements were taken before (Pre) and at two moments post-interventions (Post 1: between 30 and 60 min; Post 2: after 7 h). Ambulatory blood pressure (BP) was monitored for 24 h. At Post 1, exercise decreased systolic BP similarly in normotensives and hypertensives (-8 ± 2 vs -13 ± 2 mmHg, P > 0.05), whereas diastolic BP decreased more in hypertensives (-4 ± 1 vs -9 ± 1 mmHg, P < 0.05). Cardiac output and systemic vascular resistance did not change in normotensives and hypertensives (0.0 ± 0.3 vs 0.0 ± 0.3 L/min; -1 ± 1 vs -2 ± 2 U, P > 0.05). After exercise, heart rate (+13 ± 3 vs +13 ± 2 bpm) and its variability (low- to high-frequency components ratio, 1.9 ± 0.4 vs +1.4 ± 0.3) increased whereas stroke volume (-14 ± 5 vs -11 ± 5 mL) decreased similarly in normotensives and hypertensives (all, P > 0.05). At Post 2, all variables returned to pre-intervention, and ambulatory data were similar between sessions. Thus, a session of resistance exercise promoted PREH in normotensives and hypertensives. Although this PREH was greater in hypertensives, it did not last during the ambulatory period, which limits its clinical relevance. In addition, the mechanisms of PREH were similar in hypertensives and normotensives.

Effects of acute and chronic sleep deprivation on cardiovascular regulation.

Sleep is a fundamental physiological process, characterized by the activation of several cortical and subcortical neural networks. The relation between sleep and cardiovascular system is complex and bidirectional: sleep disorders may alter cardiovascular system, leading to an increased cardiovascular risk, while, on the contrary, cardio- vascular diseases are characterized by an alteration of physiological sleep. Autonomic nervous system (ANS) plays a key role in the regulation of cardiovascular functions during different sleep stages, with sympatho-vagal balance dynamically shifting towards sympathetic or vagal predominance across different sleep stages. Sleep deprivation (SD) has becoming one of the most relevant health problem in modern societies. SD can be related to aging, which is associated with increased sleep fragmentation, and to sleep disorders, such as sleep disordered breathing and neurological disorders. Experimental studies in animals showed that SD significantly affects cardiovascular functions, altering heart rate and blood pressure responses, and increasing sympathetic activity and neuroendocrine response to stressor stimuli. Clinical studies in humans have shown that SD, either due to experimental sleep loss and to sleep disorders, can affect different biological pathways, such as cardiovascular autonomic control, inflammation, immunity responses and metabolism. All these alterations may predispose subjects with SD to an increased cardiovascular risk. Hence, it is fundamental to identify the presence of a sleep disorder, which could be per se responsible for sleep loss, or the presence of sleep deprivation due to other factors, such as social life, habits etc., in order to identify subjects at high risk for cardiovascular events.

Predictive accuracy of triage nurses evaluation in risk stratification of syncope in the emergency department.

BACKGROUND: Syncope is a common clinical problem that accounts for 1-3% of all emergency department (ED) visits. Its prognosis is extremely variable with a 1-year mortality that may reach 30%. There are no available data about the accuracy of nursing triage in identifying high-risk syncope. The aim of our study was to evaluate the predictive accuracy of nursing triage in identifying high-risk syncope. METHODS: We conducted a retrospective study on 678 consecutive patients who presented with syncope at four EDs. For each patient, nursing triage, comorbidities, clinical features and adverse events that occurred both in the ED and at 10-day follow-up were assessed. Adverse events included death, readmission to ED, need for major therapeutic procedures, cardiopulmonary resuscitation, intensive care unit admittance, acute antiarrhythmic therapy and major causes of syncope identified during the ED evaluation. Predictive accuracy of nursing triage was evaluated. RESULTS: We observed a total of 55 (8.1%) adverse events. Eight of them (9.4%) occurred among the 85 patients who were identified as high priority by nursing triage. Sensitivity (Sn) and specificity (Sp) of urgent nursing triage in identifying adverse outcomes in the ED (19 patients) were 21% (95% CI 3% to 39%) and 88% (95% CI 85% to 90%), while the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were 1.7 and 0.9, respectively. Sn and Sp for 10-day adverse events were 15% (95% CI 5% to 24%) and 88% (95% CI 85% to 90%), respectively, with a LR+ of 1.18 and a LR- of 0.98. CONCLUSIONS: Nursing triage was characterised by a low predictive accuracy in identifying high-risk individuals.

Applied magnetic field design for the field reversed configuration compression heating experiment.

Detailed calculations of the formation, guide, and mirror applied magnetic fields in the FRC compression-heating experiment (FRCHX) were conducted using a commercially available generalized finite element solver, COMSOL Multiphysics(®). In FRCHX, an applied magnetic field forms, translates, and finally captures the FRC in the liner region sufficiently long to enable compression. Large single turn coils generate the fast magnetic fields necessary for FRC formation. Solenoidal coils produce the magnetic field for translation and capture of the FRC prior to liner implosion. Due to the limited FRC lifetime, liner implosion is initiated before the FRC is injected, and the magnetic flux that diffuses into the liner is compressed. Two-dimensional axisymmetric magnetohydrodynamic simulations using MACH2 were used to specify optimal magnetic field characteristics, and this paper describes the simulations conducted to design magnetic field coils and compression hardware for FRCHX. This paper presents the vacuum solution for the magnetic field.

Short-term complexity indexes of heart period and systolic arterial pressure variabilities provide complementary information.

It is unclear whether the complexity of the variability of the systolic arterial pressure (SAP) provides complementary information to that of the heart period (HP). The complexity of HP and SAP variabilities was assessed from short beat-to-beat recordings (i.e., 256 cardiac beats). The evaluation was made during a pharmacological protocol that induced vagal blockade with atropine or a sympathetic blockade (beta-adrenergic blockade with propranolol or central sympathetic blockade with clonidine) alone or in combination, during a graded head-up tilt, and in patients with Parkinson's disease (PD) without orthostatic hypotension undergoing orthostatic challenge. Complexity was quantified according to the mean square prediction error (MSPE) derived from univariate autoregressive (AR) and multivariate AR (MAR) models. We found that: 1) MSPE(MAR) did not provide additional information to that of MSPE(AR); 2) SAP variability was less complex than that of HP; 3) because HP complexity was reduced by either vagal blockade or vagal withdrawal induced by head-up tilt and was unaffected by beta-adrenergic blockade, HP was under vagal control; 4) because SAP complexity was increased by central sympathetic blockade and was unmodified by either vagal blockade or vagal withdrawal induced by head-up tilt, SAP was under sympathetic control; 5) SAP complexity was increased in patients with PD; and 6) during orthostatic challenge, the complexity of both HP and SAP variabilities in patients with PD remained high, thus indicating both vagal and sympathetic impairments. Complexity indexes derived from short HP and SAP beat-to-beat series provide complementary information and are helpful in detecting early autonomic dysfunction in patients with PD well before circulatory symptoms become noticeable.

Clinical and pathological heterogeneity in a series of 31 patients with IgM-related neuropathy.

BACKGROUND: IgM-related neuropathy generally presents as a late-onset demyelinating polyneuropathy with predominant sensory loss and ataxia. Sporadic cases with atypical presentation have been described. PATIENTS AND METHODS: We report clinical and pathological findings from 31 patients with IgM-related neuropathy followed in our Institute of Neurology over a 20-year period. RESULTS: Typical presentation with predominant sensory ataxic neuropathy was observed in 18/31 patients. In the remaining 13/31 (42%), we observed an atypical phenotype, characterized by multiple mononeuropathy or polyneuropathy with predominant motor impairment; one patient had polyneuropathy with predominant small-fibre involvement. Uncommon pathological findings consisting in inflammatory infiltrates, focal axonal loss or light chain deposition were observed in 8 patients, all with atypical clinical phenotype. Almost all patients with atypical phenotype improved with immunosuppressive therapy. CONCLUSIONS: A significant proportion of patients with IgM-related neuropathy presents with atypical clinical features. In these patients, sural nerve biopsy helps clarify heterogeneous disease mechanisms and identify patients who might benefit from immunosuppressive therapy.

Binary symbolic dynamics classifies heart rate variability patterns linked to autonomic modulations.

Symbolic dynamics derived from heart rate variability (HRV) is able to reflect changes of cardiac autonomic modulations on short time scales in spite of the considerable reduction of information involved. However, the link between the appearance of specific symbolic patterns and the activity of the autonomic nervous system has not yet been elucidated. In this study, we investigate the symbolic dynamics that reflect acceleration (='1') and deceleration (='0') of the instantaneous heart rate. The resulting binary series is analyzed with respect to the regularity of binary patterns of length 8 using Approximate Entropy (ApEn). Binary patterns were grouped according to the level of their regularity as assessed by ApEn. ECG recordings were obtained from 17 healthy subjects during graded head-up tilt (0, 15, 30, 45, 60, 75, and 90°). The linear correlation (Spearman correlation coefficient) between tilt angle and the occurrence of binary patterns was evaluated. The results show that regular binary patterns occurred more often with increasing tilt angle whereas the occurrence of some irregular patterns decreased. Some binary patterns did not show a change of occurrence during tilt. When compared to the results of spectral analysis, regular binary patterns reflect sympathetic modulations whereas irregular binary patterns reflect parasympathetic modulations. The parameters derived from binary symbolic dynamics reflect changes of autonomic modulations during graded head-up tilt and are not fully correlated to the spectral markers of HRV.

Spectral and symbolic analysis of the effect of gender and postural change on cardiac autonomic modulation in healthy elderly subjects

The objective of this study was to use linear and non-linear methods to investigate cardiac autonomic modulation in healthy elderly men and women in response to a postural change from the supine to the standing position. Fourteen men (66.1 ± 3.5 years) and 10 women (65.3 ± 3.3 years) were evaluated. Beat-to-beat heart rate was recorded in the supine and standing positions. Heart rate variability was studied by spectral analysis, including both low (LFnu-cardiac sympathetic modulation (CSM) indicator) and high (HFnu-cardiac vagal modulation (CVM) indicator) frequencies in normalized units as well as the low frequency/high frequency (LF/HF) ratio. Symbolic analysis was performed using the following indexes: 0V percent (CSM indicator), 1V percent (CSM and CVM indicators), 2LV percent (predominantly CVM indicator) and 2ULV percent (CVM indicator). Shannon entropy was also calculated. Men presented higher LFnu and LF/HF ratio and lower HFnu and 1V percent symbolic index (57.56, 4.14, 40.53, 45.96, respectively) than women (24.60, 0.45, 72.47, 52.69, respectively) in the supine position. Shannon entropy was higher among men (3.53) than among women (3.33) in the standing position, and also increased according to postural change in men (3.25; 3.53). During postural change, the LFnu (24.60; 49.85) and LF/HF ratio (0.45; 1.72) increased, with a concomitant decrease in HFnu (72.47; 47.56) and 2LV percent (14.10; 6.95) in women. Women presented increased CSM in response to postural change and had higher CVM and lower CSM than men in the supine position. In conclusion, women in the age range studied presented a more appropriate response to a postural change than men, suggesting that cardiac autonomic modulation may be better preserved in women than in men.

Spectral and symbolic analysis of the effect of gender and postural change on cardiac autonomic modulation in healthy elderly subjects.

The objective of this study was to use linear and non-linear methods to investigate cardiac autonomic modulation in healthy elderly men and women in response to a postural change from the supine to the standing position. Fourteen men (66.1 ± 3.5 years) and 10 women (65.3 ± 3.3 years) were evaluated. Beat-to-beat heart rate was recorded in the supine and standing positions. Heart rate variability was studied by spectral analysis, including both low (LFnu-cardiac sympathetic modulation (CSM) indicator) and high (HFnu-cardiac vagal modulation (CVM) indicator) frequencies in normalized units as well as the low frequency/high frequency (LF/HF) ratio. Symbolic analysis was performed using the following indexes: 0V% (CSM indicator), 1V% (CSM and CVM indicators), 2LV% (predominantly CVM indicator) and 2ULV% (CVM indicator). Shannon entropy was also calculated. Men presented higher LFnu and LF/HF ratio and lower HFnu and 1V% symbolic index (57.56, 4.14, 40.53, 45.96, respectively) than women (24.60, 0.45, 72.47, 52.69, respectively) in the supine position. Shannon entropy was higher among men (3.53) than among women (3.33) in the standing position, and also increased according to postural change in men (3.25; 3.53). During postural change, the LFnu (24.60; 49.85) and LF/HF ratio (0.45; 1.72) increased, with a concomitant decrease in HFnu (72.47; 47.56) and 2LV% (14.10; 6.95) in women. Women presented increased CSM in response to postural change and had higher CVM and lower CSM than men in the supine position. In conclusion, women in the age range studied presented a more appropriate response to a postural change than men, suggesting that cardiac autonomic modulation may be better preserved in women than in men.

A case of CMT 1B due to Val 102/fs null mutation of the MPZ gene presenting as hyperCKemia.

Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2). The most common demyelinating form is CMT1A, due to a duplication in the gene encoding the peripheral myelin protein 22 (PMP22). Less frequently, mutations in the myelin protein zero gene (MPZ/P0) account for demyelinating CMT1B. Herein, we report a patient presenting with an isolated hyperCKemia in whom electrophysiological and pathological findings revealed a demyelinating and axonal neuropathy. Sequencing of the MPZ gene revealed a 306delA at codon 102 in the proband and in two relatives. This mutation has been already described in association with paucisymptomatic CMT without hyperCKemia.

Information transfer through the spontaneous baroreflex in healthy humans.

OBJECTIVES: This study assesses the information transfer through the spontaneous baroreflex (i.e. through the pathway linking systolic arterial pressure to heart period) during an experimental condition soliciting baroreflex (i.e. head-up tilt). METHODS: The information transfer was calculated as the conditional entropy of heart period given systolic arterial pressure using a mutual neighbor approach and uniform quantization. The information transfer was monitored as a function of the forecasting time k. RESULTS: We found that during head-up tilt the information transfer at k = 0 decreased but the rate of rise of information transfer as a function of k was faster. CONCLUSIONS: We suggest that the characterization of the information transfer from systolic arterial pressure to heart period might complement the traditional characterization of the spontaneous baroreflex based on transfer function analysis.