Top-down brain circuits for operant bradycardia.

Heart rate (HR) can be voluntarily regulated when individuals receive real-time feedback. In a rat model of HR biofeedback, the neocortex and medial forebrain bundle were stimulated as feedback and reward, respectively. The rats reduced their HR within 30 minutes, achieving a reduction of approximately 50% after 5 days of 3-hour feedback. The reduced HR persisted for at least 10 days after training while the rats exhibited anxiolytic behavior and an elevation in blood erythrocyte count. This bradycardia was prevented by inactivating anterior cingulate cortical (ACC) neurons projecting to the ventromedial thalamic nucleus (VMT). Theta-rhythm stimulation of the ACC-to-VMT pathway replicated the bradycardia. VMT neurons projected to the dorsomedial hypothalamus (DMH) and DMH neurons projected to the nucleus ambiguus, which innervates parasympathetic neurons in the heart.

The influence of age on the psychological profile of patients with cardiac implantable electronic devices: results from the Italian population in a multicenter study conducted by the European Heart Rhythm Association.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) are widely used to treat bradyarrhythmias or improve the prognosis of patients with heart failure (HF). AIMS: To evaluate age-related (≤ 75 vs. > 75 years) attitudes, worries, psychological effects and needs in an Italian CIEDs population. METHODS: Patients attending their periodical ambulatory evaluation received a questionnaire conceived by the European Heart Rhythm Association Scientific Initiatives Committee as part of a multicenter, multinational snapshot survey. Seven countries participated in the study, and 1646 replies were collected. Of these, 437 (27%) were from Italy. Present results refer to the Italian population only. CIEDs were stratified into devices to treat bradycardia or HF. RESULTS: The use of CIEDs was more common in advanced age. Older patients needed less information about CIEDs than younger ones (p = 0.044), who would prefer to be better informed about CIEDs-related consequences on psychologic profile (p = 0.045), physical (p < 0.001) and sexual (p < 0.001) activities, and driving limitations (p = 0.003). When compared to older subjects, younger individuals experienced more difficulties (p = 0.035), especially in their professional (p < 0.001) and private life (p = 0.033), feeling their existence was limited by the device (p < 0.001). Conversely, quality of life (HRQL) more often improved in the elderly (p = 0.001). Information about what to do with CIEDs at the end of life is scant independently of age. CONCLUSIONS: HRQL after CIEDs implantation improves more frequently in older patients, while the psychological burden of CIEDs is usually higher in younger patients. End of life issues are seldom discussed.

Electrocardiographic characteristics in individuals with cocaine use disorder.

BACKGROUND AND OBJECTIVES: Chronic cocaine use has been linked to several abnormalities in cardiac functioning. The objective of this study was to further characterize baseline heart rate and electrocardiograph (ECG) profiles of individuals with cocaine use disorder (CUD) by evaluating demographic and drug use variables that may impact cardiovascular profiles. METHODS: Participants with CUD (n = 335, primarily African-American males) provided demographic and drug use data and ECG profiles (eg, heart rate, PR Interval, QRS, and QTc) were obtained via 12-lead ECG. RESULTS: Forty-eight percent and ten percent of cocaine users met criteria for sinus bradycardia (heart rate ≤60) and severe bradycardia (heart rate ≤50), respectively. Females had significantly higher heart rate (p = .020, d = .30) and QTc (p < .001, d = .75) and significantly lower QRS (p = .002, d = .42) in comparison to males. Those who were cocaine positive had higher QTc (p = .025, d = .26) with a higher prevalence of bradycardia (chi-square = 3.91, p = .048) than those who were negative. Cocaine users who also used alcohol had significantly lower PR Interval (p = .003, d = .36), QRS (p = .014, d = .29), and QTc (p = .037, d = .25) than those who denied alcohol use. CONCLUSIONS: These findings characterize the baseline heart rate and ECG profiles of individuals with CUD, confirm previous reports of cocaine-induced alterations in cardiovascular function, and demonstrate factors impacting cardiovascular profiles. SCIENTIFIC SIGNIFICANCE: While exploratory, these results suggest the presence of bradycardia may serve as a useful biomarker for initiating therapy for individuals with CUD and averting potential adverse cardiovascular events. Future prospective studies are needed to assess this possibility. (Am J Addict 2017;26:221-227).

Modeling fear-conditioned bradycardia in humans.

Across species, cued fear conditioning is a common experimental paradigm to investigate aversive Pavlovian learning. While fear-conditioned stimuli (CS+) elicit overt behavior in many mammals, this is not the case in humans. Typically, autonomic nervous system activity is used to quantify fear memory in humans, measured by skin conductance responses (SCR). Here, we investigate whether heart period responses (HPR) evoked by the CS, often observed in humans and small mammals, are suitable to complement SCR as an index of fear memory in humans. We analyze four datasets involving delay and trace conditioning, in which heart beats are identified via electrocardiogram or pulse oximetry, to show that fear-conditioned heart rate deceleration (bradycardia) is elicited and robustly distinguishes CS+ from CS-. We then develop a psychophysiological model (PsPM) of fear-conditioned HPR. This PsPM is inverted to yield estimates of autonomic input into the heart. We show that the sensitivity to distinguish CS+ and CS- (predictive validity) is higher for model-based estimates than peak-scoring analysis, and compare this with SCR. Our work provides a novel tool to investigate fear memory in humans that allows direct comparison between species.

Psychophysiological evidence for the role of emotion in adaptive memory.

Studies demonstrating a mnemonic benefit for encoding words in a survival scenario have revived interest in how human memory is shaped by evolutionary pressures. Prior work on the survival-processing advantage has largely examined cognitive factors as potential proximate mechanisms. The current study, by contrast, focused on the role of perceived threat. Guided by the idea that a survival scenario implies threat, we combined measures of heart rate (HR) with affective ratings to probe the potential presence of fear bradycardia as a marker of freezing--a parasympathetically dominated HR deceleration that reflects the initial stage of the defensive engagement. We replicated the mnemonic advantage in behavior and found that the survival scenario was rated higher in perceived negative arousal than a commonly used control scenario. Critically, words encountered in the survival scenario were associated with more extensive HR deceleration, and this effect was directly related to subsequent recall performance. Our findings point to a role for the involvement of neurobiological fear responses in producing the survival processing advantage, as well as potential links between autonomic changes and cognitive processing in adaptive memory.

Long term quality-of-life in patients with bradycardia pacemaker implantation.

BACKGROUND: Health-related quality of life (HRQoL) values shortly after pacemaker (PM) implantation for bradycardia have been established, however little is known about long-term HRQoL. METHODS: Using the generic SF-36 and the PM specific Aquarel questionnaire, HRQoL was repeatedly measured during a 7.5 year follow-up period in 881 bradycardia PM recipients included in the large scale nationwide Dutch FOLLOWPACE study. HRQoL over time, corrected for age, gender, diabetes, hypertension, heart failure, cardiovascular disease and AV-synchrony, was assessed with a linear mixed model. RESULTS: Increased scores both on overall SF-36 and on all SF-36 subscales were observed shortly after implantation. Although scores on SF-36 gradually declined over time, scores remained improved over the measured pre-implantation values. Also, scores for almost all subscales remained increased throughout the 7.5 year observation period, except for physical functioning which showed a gradual decline several years after the initial rise. Additionally, higher scores on all Aquarel scales were observed after implantation. Scores on the arrhythmias and chest discomfort subscales improved and remained stable throughout follow-up (FU), whereas the dyspnea at exertion subscale showed a gradual decline during FU to reach pre-implantation values at 5 years. CONCLUSIONS: Increased HRQoL is observed not only shortly after PM implantation, but also after long-term FU. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00135174; http://www.clinicaltrials.gov/ct2/show/NCT00135174.

Chronic angiotensin-II treatment potentiates HR slowing in Sprague-Dawley rat during acute behavioral stress.

This study examined the effect of 2-week infusion of angiotensin-II (Ang-II; 175 ng/kg/min) via minipump in rats (n=7) upon the mean arterial blood pressure (mBP) and heart rate (HR) response to an acute stress as compared to rats infused with saline (n=7). The acute stress was produced by a classical aversive conditioning paradigm: a 15s tone (CS+) followed by a half second tail shock. Baseline mBP in Ang-II infused rats (167.7±21.3 mm Hg; mean±SD) significantly exceeded that of controls (127.6±13.5 mm Hg). Conversely, baseline HR in the Ang-II infused rats (348±33) was significantly lower than controls (384±19 bpm). The magnitude of the mBP increase during CS+ did not differ between groups, but the HR slowing during CS+ in the Ang-II infused rats (-13.2±8.9 bpm) was significantly greater than that seen in controls (-4.2±5.5 bpm). This augmented bradycardia may be inferentially attributed to an accentuated increase in cardiac parasympathetic activity during CS+ in the Ang-II infused rats. The mBP increased above baseline immediately post-shock delivery in controls, but fell in the Ang-II infused rats, perhaps because of a 'ceiling effect' in total vascular resistance. This classical conditioning model of 'acute stress' differs from most stress paradigms in rats in yielding a HR slowing concomitant with a pressor response, and this slowing is potentiated by Ang-II.

Stimulus appraisal modulates cardiac reactivity to briefly presented mutilation pictures.

Emotional reactions to threatening situations can be either advantageous for human adaptation or unfavorable for physical and mental health if sustained over prolonged periods of time. These contrasting effects mostly depend on the individual's capacity for emotion regulation. It has been shown, for example, that changing appraisal can alter the course of emotional processing. In the present study, the influence of stimulus appraisal over cardiac reactivity to briefly presented (200ms) mutilation pictures was tested in the context of an affective classification task. Heart rate and reaction time of twenty-four undergraduate students were monitored during the presentation of pictures (neutral or mutilated bodies) in successive blocks. In one condition (real), participants were told that the pictures depicted real events. In the other condition (fictitious), they were told that the pictures were taken from movie scenes. As expected, the results showed a more pronounced bradycardia to mutilation pictures, in comparison to neural pictures, in the real context. In the fictitious context, a significant attenuation of the emotional modulation (defensive bradycardia) was observed. However, this attenuation seemed to be transient because it was only observed in the first presentation block of the fictitious context. Reaction time to classify mutilation pictures, compared to neutral pictures, was slower in both contexts, reflecting the privileged processing of emotionally laden material. The present findings show that even briefly presented mutilation pictures elicit a differential cardiac reactivity and modulate behavioral performance. Importantly, changing stimulus appraisal attenuates the emotional modulation of cardiac reactivity (defensive bradycardia).

Pacemaker patients' perception of unsafe activities: a survey.

BACKGROUND: Cardiac pacing is a recognized and widely used treatment for patients presenting with bradycardia. Physicians expect patients to return to normal activities almost immediately post implantation. However, patients themselves may perceive interference to pacemaker function by various routine activities and devices, and hence continue to lead restricted, disabled lives. The aim of this study is to determine if routine activities are perceived by pacemaker patients to interfere with their device function. METHODS: A descriptive cross sectional survey was carried out on consecutive patients at the pacemaker clinic at a public hospital in Karachi, Pakistan. A 47-question tool was developed and tested. Patients' perceptions of safety of performing various routine activities, along with socio-demographic data were recorded. RESULTS: The final sample included 93 adult patients (45% males). 41% were illiterate. 77.4% recalled receiving counselling at implantation, predominantly from the implanting physician and house staff. A considerable proportion of patients considered many routine activities unsafe including driving automobiles (28%), passing through metal detectors (31%), bending over (37%), and sleeping on the side of the pacemaker (30%). Also considered unsafe were operation of household appliances--TV/VCR (television/video cassette recorders) (53%), irons (55%)) and electrical wall switches (56%). For nearly all variables neither literacy nor history of counselling improved incorrect perceptions. CONCLUSION: This study shows that our pacemaker patients perceive many routine activities as unsafe, potentially leading to disabling life style modifications. The tremendous investment in pacemaker technology to improve patient performance is not going to pay dividends if patients continue to remain disabled due to incorrect perceptions. Further studies are required to determine the reasons for these misperceptions, and to determine if these problems also exist in, and hinder, other patient populations.

Catatonic coma with profound bradycardia.

Catatonia may be monosymptomatic at presentation, with stupor or coma as the cardinal and only manifestation. A case of catatonic coma with profound bradycardia is presented to help clinicians recognize this entity and include catatonia in the differential diagnosis of coma as a rare etiology after other more common causes of coma have been excluded. Cases of catatonic coma are nevertheless important to identify because treatment with intravenous benzodiazepines is simple and highly effective. The authors argue that the descriptive term "catatonic coma" is preferable over terms implying psychogenesis, such as "psychogenic" or "hysterical" coma; for catatonia, the authors have a specific treatment, in the form of benzodiazepines; for "psychogenesis," there is none.

A freezing-like posture to pictures of mutilation.

Postural sway and heart rate were recorded in young men viewing emotionally engaging pictures. It was hypothesized that they would show a human analog of "freezing" behavior (i.e., immobility and heart rate deceleration) when confronted with a sustained block of unpleasant (mutilation) images, relative to their response to pleasant/arousing (sport action) or neutral (objects) pictures. Volunteers stood on a stabilometric platform during picture viewing. Significantly reduced body sway was recorded during the unpleasant pictures, along with increased mean power frequency (indexing muscle stiffness). Heart rate during unpleasant pictures also showed the expected greater deceleration. This pattern resembles the "freezing" and "fear bradycardia" seen in many species when confronted with threatening stimuli, mediated by neural circuits that promote defensive survival.

Recurrent symptomatic bradycardia due to secret ingestion of beta-blockers--a rare manifestation of cardiac Münchhausen syndrome.

The term Münchhausen syndrome was established in 1951 by Asher to describe a severe psychiatric illness in which patients simulate false symptoms and signs. We report on a female general practitioner who repeatedly ingested high doses of beta-blockers in order to simulate symptomatic sick-sinus syndrome. She had been admitted to intermediate care units in several hospitals before the correct diagnosis was made by finding the tablets in her toilet bag. Following psychiatric exploration and psychotherapy, she has been working in her community again for about a year. This is the first report on the clinical presentation and course of disease in a patient with cardiac Münchhausen syndrome who secretly ingested beta-blockers to provoke a menacing bradycardia. The follow-up indicates that frequent and intense symptomatic episodes of this remarkable psychiatric disease can be interrupted by long normal intervals.

Cardiorespiratory events detected by home memory monitoring and one-year neurodevelopmental outcome.

OBJECTIVE: To determine if infants with cardiorespiratory events detected by home memory monitoring during early infancy have decreased neurodevelopmental performance. STUDY DESIGN: Infants (n = 256) enrolled in the Collaborative Home Infant Monitoring Evaluation also completed the Bayley Scales of Infant Development II at 92 weeks' postconceptional age. Infants were classified as having 0, 1 to 4, or 5+ cardiorespiratory events. Events were defined as apnea >or=20 seconds or heart rate <60 to 80 bpm or <50 to 60 bpm, for >or=5 to 15 seconds, depending on age. RESULTS: For term infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean Mental Developmental Index (MDI) values (+/-SD) of 103.6 (10.6), 104.2 (10.7), and 97.7 (10.9), respectively, and mean Psychomotor Developmental Index (PDI) values of 109.5 (16.6), 105.8 (16.5), and 100.2 (17.4). For preterm infants, having 0, 1 to 4, and 5+ cardiorespiratory events was associated with unadjusted mean MDI values of 100.4 (10.3), 96.8 (11.5), and 95.8 (10.6), respectively, and mean PDI values of 91.7 (19.2), 93.8 (15.5), and 94.4 (17.7). The adjusted difference in mean MDI scores with 5+ events compared with 0 events was 5.6 points lower in term infants ( P = .03) and 4.9 points lower in preterm infants ( P = .04). CONCLUSIONS: Having 5+ conventional events is associated with lower adjusted mean differences in MDI in term and preterm infants.

[Heart disease in schizophrenia]. / Kardiale Erkrankung bei Schizophrenie.

A 63-year-old male patient diagnosed with chronic schizophrenia and characterized by formal disorders of thought with neologism and paranoid ideation, especially grandiose delusions and feelings of being influenced by radiation, is presented. At admission to psychiatric hospital, the patient reported attacks of weakness and dizziness, which he attributed to his feelings of alien influence. The diagnosis of cardiac disease with severe bradycardia could already be established by basic physical examination. Further diagnostic procedures (e.g., ECG) revealed symptomatic atrioventricular conduction defects (atrioventricular block III). After implantation of a cardiac pacemaker, the somatic symptoms vanished and the patient recovered completely in terms of physical condition.

Psychometric properties of Aquarel. a disease-specific quality of life questionnaire for pacemaker patients.

In cardiac pacing current clinical practice permits the use of ventricular or atrioventricular-synchronous pacemakers. However, it is not known which type of pacemaker results in superior clinical and patient outcomes. To date, there is no feasible and validated disease-specific questionnaire for pacemaker patients to assess quality of life (QoL) available. The Aquarel questionnaire was developed as a disease-specific extension to the Short-Form-36 (SF-36). A cross-sectional study was carried out in 74 pacemaker patients to evaluate validity and reliability of this instrument. Items were selected and scales constructed based on factorial analysis. Internal consistency, content validity and test-retest reliability were moderate to excellent. Correlations with the SF-36 scales, pacing mode and functional tests were as hypothesized, demonstrating the individual value and distinctiveness of the Aquarel subscales. The results support the feasibility and usefulness of evaluating QoL in pacemaker patients when using Aquarel as an extension to the SF-36.

Improvement of cerebral blood flow and cognitive function following pacemaker implantation in patients with bradycardia.

We investigated the effects of pacemaker implantation on cerebral blood flow and cognitive function in 14 severely bradycardic patients (mean age 75.2 years). Cerebral blood flow and verbal intelligence improved after the pacemaker implantation. Systolic and mean arterial blood pressure was significantly reduced after the implantation. Changes in cerebral blood flow significantly correlated with changes in heart rate in polynomial regression analysis, but not with changes in cardiac output. Before the implantation, verbal cognitive function was lower in bradycardic patients than in age-matched control subjects, and brain CT showed significant advanced atrophy in these patients. However, verbal cognitive function was also improved after the implantation. Pacemaker implantation in the severe bradycardic elderly should be beneficial not only for cardiac function but also for brain function. We concluded that these results suggest that heart rate is one of the important factors in the regulation of cerebral circulation in patients with severe bradycardia. Pacemaker implantation in the elderly improved quality of life and may prevent mental deterioration.

[Effect of adaptation to continuous stress on the contractile function and electric stability of the heart]. / Vliianie adaptatsii i nepreryvnomu stressornomu vozdeistviiu na sokratitel'nuiu funktsiiu i élektricheskuiu stabil'nost' serdtsa.

In the time course of 15-day stress of moderate intensity, rat experiments indicated that following a day there developed a complex of changes typical of acute stressor syndrome. Five days of post-stress , the stress-related cardiac syndrome ceased, bradycardia developed, the contractile function was limited, and the fibrillation threshold returned to the control values, which was shown to be associated with activation of the cholinergic stress-limiting system. Fifteen days later there was normalization of heart rate and cardiac contractility, the fibrillation threshold remained at the baseline level.