Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

Background: Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. Objective: The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods: In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results: In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P,0.05). Conclusion: In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity

Possible predicative role of electrical risk score on transcatheter aortic valve replacement outcomes in older patients. preliminary data

Background:Transcatheter aortic valve replacement (TAVR) is an effective procedure capable to change the natural history of the degenerative aortic valve stenosis. Despite the TAVR, the patients with advanced valve disease and severe myocardial damage (low flow, gradient and ejection fraction)show high mortality level. Aim of this study was toevaluate the predicative power of a noninvasive and inexpensive test obtained by means of a simple standard 12-leads electrocardiogram,known as the Electrical Risk Score (ERS). Methods: ERS was composed by seven simple ECG markers: heart rate (>75 bpm); QRS duration (>110 ms), left ventricular hypertrophy (Sokolow-Lyon criteria), delayed QRS transition zone (≥ V4), frontal QRS-T angle (>90°), long QTBazett (>450 ms for men and >460 in women) or JTBazett(330 ms for men and > 340 ms for women);long T peak to T end interval (Tp-e)( >89 ms). An ERS ≥ 4was considered high risk for all-cause or cardiovascular mortality.We calculated retrospectively the pre-procedure ERS in 40 TAVR patients after one year of follow-up. Results: In the follow up the all-cause and cardiovascular mortality were respectively 25% and 15%.None of survivors reported ERS ≥ 4,moreover, the ERS was the strongest predictor of all-cause (odd ratio 3.73, 95% CI: 1.44-9.66, p<0.05) or cardiovascular (odd ratio 3.95, 95% CI: 1.09-14.27, p<0.05) mortality.ROC curves showed that ERS had the widest significant sensitivity-specificity area under the curve (auc) predicting all-cause (auc: 0.855, p<0.05) or cardiovascular mortality (auc: 0.908, p<0.05). Conclusions:In this pivotal study, ERS resulted an useful tool to stratify the risk of mortality in one-year follow-up TAVR patients. Obviously, it is necessary to confirm these data in large prospective studies

Arrhythmic risk in elderly patients candidates to transcatheter aortic valve replacement. predicative role of repolarization temporal dispersion

Degenerative aortic valve stenosis (AS) is associated to ventricular arrhythmias and sudden cardiac death, as well as mental stress in specific patients. In such a context, substrate, autonomic imbalance as well as repolarization dispersion abnormalities play an undoubted role. Aim of the study was to evaluate the increase of premature ventricular contractions (PVC) and complex ventricular arrhythmias during mental stress in elderly patients candidate to the transcatheter aortic valve replacement (TAVR). In eighty-one elderly patients with AS we calculated several short-period RRand QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE). All the myocardial repolarization dispersion markers worsened during mental stress (p &lt; 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p &lt; 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p &lt; 0.05). Eventually, twenty-four (30%) and twelve (15%) patients increased significantly PVC and, respectively, complex ventricular arrhythmias during the MMSE administration. At multivariate logistic regression analysis, the standard deviation of QTend (QTesd), obtained at rest, was predictive of increased PVC (odd ratio: 1.54, 95% CI 1.14–2.08; p = 0.005) and complex ventricular arrhythmias (odd ratio: 2.31, 95% CI 1.40–3.83; p = 0.001) during MMSE. The QTesd showed the widest sensitive-specificity area under the curve for the increase of PVC (AUC: 0.699, 95% CI: 0.576–0.822, p &lt; 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p &lt; 0.05). In elderly with AS ventricular arrhythmias worsened during a simple cognitive assessment, this events being a possible further burden on the outcome of TAVR. QTesd might be useful to identify those patients with the highest risk of ventricular arrhythmias. Whether the TAVR could led to a QTesd reduction and, hence, to a reductionof thearrhythmicburdenin thissettingofpatients isworthytobe investigated

Oscillatory behavior of P wave duration and PR interval in experimental congestive heart failure: a preliminary study

Objective: The relationship between the autonomic nervous system (ANS) modulation of the sinus node and heart rate variability has been extensively investigated. The current study sought to evaluate, in an animal experimental model of pacing-induced tachycardia congestive heart failure (CHF), a possible ANS influence on the P wave duration and PR interval oscillations. Approach: Short-term (5 min) time and frequency domain analysis has been obtained in six dogs for the following electrocardiographic intervals: P wave duration (P), from the onset to peak of P wave (P p), from the onset of P wave to the q onset (PR) and from the end of P wave to the onset of q wave (P e R). Direct vagal nerve activity (VNA), stellate ganglion nerve activity (SGNA) and electrocardiogram (ECG) intervals have been evaluated contextually by implantation of three bipolar recording leads. Main results: At the baseline, multiple regression analysis pointed out that VNA was strongly positively associated with the standard deviation of PP and P e R intervals (r 2:0.997, p < 0.05). The same variable was also positively associated with high-frequency (HF) of P expressed in normalized units, of P p, and of P e R (b: 0.001) (r 2: 0.993; p < 0.05). During CHF, most of the time and frequency domain variability significantly decreased from 20% to 50% in comparison to the baseline values (p < 0.05) and SGNA correlated inversely with the low frequency (LF) obtained from P e R (p < 0.05) and PR (p < 0.05) (r 2:0.899, p < 0.05). LF components, expressed in absolute and normalized power, obtained from all studied intervals, were reduced significantly during CHF. Any difference between the RR and PP spectral components was observed. Significance: The data showed a significant relationship between ANS and atrial ECG variables, independent of the cycle duration. In particular, the oscillations were vagal mediated at the baseline, while sympathetic mediated during CHF. Whereas P wave variability might have a clinical utility in CHF management, it needs to be addressed in specific studies

Interplay of cell-cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity.

Cell-cell and cell-matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals. We also demonstrate by in vivo fate mapping and clonal analysis of cardiac progenitors that cardiac fat and a subset of cardiac muscle arise from a common precursor expressing Isl1 and Wt1 during heart development, suggesting related mechanisms of determination between the two lineages

Frailty and hyperactive delirium in hospitalized older patients with COVID-19: an insight from GeroCovid registry

Background: Delirium is an acute neuropsychiatric condition associated with unfavourable outcomes, frequent in older hospitalized people. In the context of the SARS-CoV-2 pandemic, few studies have specifically focused on the inflammatory status of older, frail patients with hyperactive delirium (HD) hospitalized for COVID-19. Aim: To identify biological correlates of HD at hospital admission and to assess the independent effect of delirium and physical frailty on in-hospital mortality. Methods: Data were retrospectively extracted by the multicenter registry GeroCovid Observational Study. Individuals aged ≥ 60 years were included if the information on the presence of HD, frailty based on the modified Fried criteria and inflammatory status had been collected. The risk of mortality was evaluated using a Kaplan-Meier estimator, according to frailty and delirium. Logistic and restricted cubic-spline regressions were employed to assess the relationship between inflammatory markers and HD. Results: Three-hundred-thirty-seven older adults were included in the analysis [mean age (SD) 77.1 (9.5) years, 50.1% females], and 11.5% presented with HD. A significant association of both PaO2/FiO2 ratio (p = 0.015) and serum lactate dehydrogenase (p = 0.04) with delirium was observed. By Cox multivariable regression, frail and non-frail patients with HD had a 4.42 and 2.85 higher mortality risk compared with non-frail, non-delirious patients. Conclusions: Hyperactive delirium at hospital admission is related with markers of lung failure among older adults, especially when physical frailty coexists. Delirium is associated with increased in-hospital mortality risk, which is doubled by the coexistence of physical frailty

Investigating the Effects of a Focal Muscle Vibration Protocol on Sensorimotor Integration in Healthy Subjects

Background: The ability to perceive two tactile stimuli as asynchronous can be measured using the somatosensory temporal discrimination threshold (STDT). In healthy humans, the execution of a voluntary movement determines an increase in STDT values, while the integration of STDT and movement execution is abnormal in patients with basal ganglia disorders. Sensorimotor integration can be modulated using focal muscle vibration (fMV), a neurophysiological approach that selectively activates proprioceptive afferents from the vibrated muscle. Method: In this study, we investigated whether fMV was able to modulate STDT or STDT–movement integration in healthy subjects by measuring them before, during and after fMV applied over the first dorsalis interosseous, abductor pollicis brevis and flexor radialis carpi muscles. Results: The results showed that fMV modulated STDT–movement integration only when applied over the first dorsalis interosseous, namely, the muscle performing the motor task involved in STDT–movement integration. These changes occurred during and up to 10 min after fMV. Differently, fMV did not influence STDT at rest. We suggest that that fMV interferes with the STDT–movement task processing, possibly disrupting the physiological processing of sensory information. Conclusions: This study showed that FMV is able to modulate STDT–movement integration when applied over the muscle involved in the motor task. This result provides further information on the mechanisms underlying fMV, and has potential future implications in basal ganglia disorders characterized by altered sensorimotor integration

Depression in People With Dementia and Caregiver Outcomes : Results From the European Right Time Place Care Study

Objective: To investigate the cross-sectional associations between depression in people with dementia and both caregiver burden and quality of life in 8 European countries, and to test these associations compared with the presence of other neuropsychiatric symptoms. Design: Cross-sectional study. Setting and Participants: In total, 1223 dyads comprised of informal caregivers and people with dementia living in a community-dwelling setting, recruited from the Right Time Place Care study, a cohort survey from 8 European countries. Measures: To test the associations between depression (according to the Cornell Scale for Depression in Dementia) and informal caregiver burden (defined by the Zarit scale and hours of supervision in terms of Resource Utilization in Dementia), distress (defined by the Neuropsychiatric Inventory Questionnaire distress score), and quality of life (according to the visual analogue scale and 12-item General Health Questionnaire). Results: Linear regressions showed an association between depression and main outcomes (Zarit scale: β 3.7; P = .001; hours of supervision: β 1.7; P = .004; Neuropsychiatric Inventory Questionnaire distress score: β 1.2; P = .002). A similar association was found concerning psychological and overall well-being (12-item General Health Questionnaire: β 1.8; P < .001; Euroqol Visual Analogue Scale: β −4.1; P = .003). Both associations remained significant despite the presence of other NPS and after adjusting for confounders. Conclusions and Implications: Further studies are needed to assess whether providing tailored strategies for optimizing diagnosis and managing of depression in people with dementia might improve caregiver quality of life and reduce their burden in the community-dwelling setting