Electrophysiology and 3D-imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation.

Altered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown. Here we have addressed this knowledge gap in human GP neuron structure and physiology in patients with and without AF. Human right atrial GP neurons embedded in epicardial adipose tissue were excised during open heart surgery performed on both non-AF and AF patients and then characterised physiologically by whole cell patch clamp techniques. Structural analysis was also performed after fixation at both the single cell and at the entire GP levels via three-dimensional confocal imaging. Human GP neurons were found to exhibit unique properties and structural complexity with branched neurite outgrowth. Significant differences in excitability were revealed between AF and non-AF GP neurons as measured by lower current to induce action potential firing, a reduced occurrence of low action potential firing rates, decreased accommodation and increased synaptic density. Visualisation of entire GPs showed almost all neurons are cholinergic with a small proportion of noradrenergic and dual phenotype neurons. Phenotypic distribution differences occurred with AF including decreased cholinergic and dual phenotype neurons, and increased noradrenergic neurons. These data show both functional and structural differences occur between GP neurons from patients with and without AF, highlighting that cellular plasticity occurs in neural input to the heart that could alter autonomic influence on atrial function. KEY POINTS: The autonomic nervous system plays a critical role in regulating heart rhythm and the initiation of AF; however, the structural and functional properties of human autonomic neurons in the autonomic ganglionated plexi (GP) remain unknown. Here we perform the first whole cell patch clamp electrophysiological and large tissue confocal imaging analysis of these neurons from patients with and without AF. Our data show human GP neurons are functionally and structurally complex. Measurements of action potential kinetics show higher excitability in GP neurons from AF patients as measured by lower current to induce action potential firing, reduced low firing action potential rates, and decreased action potential accommodation. Confocal imaging shows increased synaptic density and noradrenergic phenotypes in patients with AF. Both functional and structural differences occur in GP neurons from patients with AF that could alter autonomic influence on atrial rhythm.

Reverse re-modelling chronic heart failure by reinstating heart rate variability.

Heart rate variability (HRV) is a crucial indicator of cardiovascular health. Low HRV is correlated with disease severity and mortality in heart failure. Heart rate increases and decreases with each breath in normal physiology termed respiratory sinus arrhythmia (RSA). RSA is highly evolutionarily conserved, most prominent in the young and athletic and is lost in cardiovascular disease. Despite this, current pacemakers either pace the heart in a metronomic fashion or sense activity in the sinus node. If RSA has been lost in cardiovascular disease current pacemakers cannot restore it. We hypothesized that restoration of RSA in heart failure would improve cardiac function. Restoration of RSA in heart failure was assessed in an ovine model of heart failure with reduced ejection fraction. Conscious 24 h recordings were made from three groups, RSA paced (n = 6), monotonically paced (n = 6) and heart failure time control (n = 5). Real-time blood pressure, cardiac output, heart rate and diaphragmatic EMG were recorded in all animals. Respiratory modulated pacing was generated by a proprietary device (Ceryx Medical) to pace the heart with real-time respiratory modulation. RSA pacing substantially increased cardiac output by 1.4 L/min (20%) compared to contemporary (monotonic) pacing. This increase in cardiac output led to a significant decrease in apnoeas associated with heart failure, reversed cardiomyocyte hypertrophy, and restored the T-tubule structure that is essential for force generation. Re-instating RSA in heart failure improves cardiac function through mechanisms of reverse re-modelling; the improvement observed is far greater than that seen with current contemporary therapies. These findings support the concept of re-instating RSA as a regime for patients who require a pacemaker.

Trauma-Focused Cognitive Behavioral Therapy in 13 Urban Public Schools: Mixed Methods Results of Barriers, Facilitators, and Implementation Outcomes.

Trauma-focused cognitive behavioral therapy (TF-CBT) is an evidence-based intervention to treat Post-traumatic Stress Disorder among youth ages 3-18 years. In this pilot study, 31 clinicians in 13 urban public schools received TF-CBT training to improve access to a high-quality trauma treatment for youth in need. A mixed methods design was used to assess implementation barriers, facilitators and outcomes to examine initial feasibility, acceptability, and appropriateness of TF-CBT delivered in school settings. Although 70% of clinicians reported confidence in the evidence-base of TF-CBT and its potential to support their students who have a very high prevalence of lifetime trauma exposure, implementation practice outcomes suggest a wide range of TF-CBT use (Range = 0 to 11 students enrolled per clinician, Mean = 1.4 students) with 23 clinicians implementing the TF-CBT model with at least one case. Results point to the potential value of training school mental health clinicians in TF-CBT based on its compatibility with student needs. Yet, by connecting focus group results to top-rated barriers and facilitators, we identify several adjustments that should be made to improve intervention-setting fit in future studies. Specifically, school setting-specific intervention adaptations, school-tailored implementation support and thoughtful consideration of school-based clinicians' roles and responsibilities are needed to enhance future implementation success.

Pacemaker Use in New Zealand - Data From the New Zealand Implanted Cardiac Device Registry (ANZACS-QI 15).

BACKGROUND: The New Zealand Cardiac Implanted Device Registry (Device) has recently been developed under the auspices of the New Zealand Branch of the Cardiac Society of Australia and New Zealand. This study describes the initial Device registry cohort of patients receiving a new pacemaker, their indications for pacing and their perioperative complications. METHODS: The Device Registry was used to audit patients receiving a first pacemaker between 1st January 2014 and 1st June 2015. RESULTS: We examined 1611 patients undergoing first pacemaker implantation. Patients were predominantly male (59%), and had a median age of 70 years. The most common symptom for pacemaker implantation was syncope (39%), followed by dizziness (30%) and dyspnoea (12%). The most common aetiology for a pacemaker was a conduction tissue disorder (35%), followed by sinus node dysfunction (22%). Atrioventricular (AV) block was the most common ECG abnormality, present in 44%. Dual chamber pacemakers were most common (62%), followed by single chamber ventricular pacemakers (34%), and cardiac resynchronisation therapy - pacemakers (CRT-P) (2%). Complications within 24hours of the implant procedure were reported in 64 patients (3.9%), none of which were fatal. The most common complication was the need for reoperation to manipulate a lead, occurring in 23 patients (1.4%). CONCLUSION: This is the first description of data entered into the Device registry. Patients receiving a pacemaker were younger than in European registries, and there was a low use of CRT-P devices compared to international rates. Complications rates were low and compare favourably to available international data.

Implantable cardioverter-defibrillators: a long-term view.

BACKGROUND: No long-term data on implantable cardioverter-defibrillators (ICDs) exist in Australasia. AIMS: We examined all patients receiving a new ICD implant at Wellington Hospital between January 2001 and December 2005 to determine long-term outcomes in this patient population. METHODS: Follow-up data were collected and Kaplan-Meier curves were constructed for survival and long-term outcomes, and Cox proportional hazard model was used for calculation of hazard ratio. RESULTS: In the study period, 138 new ICDs were implanted, and the mean follow-up time was 84 ± 16 months. Patients were predominantly male (76%), 75% were European, 20% were Maori. Median age was 59 years (range 16-80 years). In 47% of patients, there was an ischaemic substrate. A secondary-prevention indication was present in 77%. The 7-year survival rate was 72%. No difference in mortality was observed between primary- and secondary-prevention groups. The 7-year appropriate therapy rate was 55%. The appropriate shock rate was greater in secondary prevention than in primary-prevention patients was observed (hazard ratio = 2.11, 95% confidence interval 1.16-3.85, P= 0.01). Over the study period, inappropriate therapy rate was 25%. This was more common in patients with prior atrial fibrillation (hazard ratio = 3.57, 95% confidence interval 1.80-7.09, P < 0.001). The median device longevity was 6.8 years. CONCLUSIONS: This is the first long-term follow-up study of ICD patients in New Zealand. We observed a low mortality rate when compared with other published registries, but a similar rate of both appropriate and inappropriate shock therapy.

Use of tunnelled active fixation leads allows reliable temporary pacing over prolonged periods.

Temporary tunnelled pacing (TTP) is an alternative method of providing temporary pacing in which an active fixation permanent pacing lead is placed fluoroscopically through percutaneous venous access, tunnelled subcutaneously and connected to a resterilized external pulse generator. Our study shows that temporary tunnelled pacing is a safe and reliable method of achieving prolonged temporary pacing. We believe that temporary tunnelled pacing should be considered as an option in all patients who have an indication for prolonged temporary pacing.

Psychological implications of ICD implantation in a New Zealand population.

AIMS: Previous studies have raised concerns about high levels of anxiety and depression in implanted cardioverter-defibrillator patients, and suggested that adverse psychological outcomes have been related to delivered therapy, age, and gender. This study aimed to assess the prevalence of anxiety and depression and to analyse quality-of-life in a New Zealand patient group. METHODS AND RESULTS: We questioned 46 ICD and 49 pacemaker patients regarding device and treatment satisfaction, depression, anxiety (Hospital Anxiety and Depression Scale), and quality-of-life (SF 36). The prevalence of clinical depression and anxiety in the ICD group was 7 and 13%, respectively, and did not differ from the pacemaker group. ICD patients mean anxiety and depression scores did not differ from the pacemaker group, although more ICD patients had subclinical levels of anxiety. Quality-of-life scores were normal for all ICD patients with respect to both mental and physical component scores, and not different from the pacemaker group. Anxiety, depression, and quality-of-life scores were unrelated to time from implantation, delivered therapy, age, or gender. Overall, 93% of the ICD patients thought their device was worthwhile. CONCLUSION: We found a lower than expected level of anxiety and depression in ICD patients, and suggest that this may be due in part to the small team approach adopted locally in the follow-up of this patient group.

Abnormal glucose metabolism and features of the metabolic syndrome are common in patients presenting for elective cardiac catheterization.

BACKGROUND: Abnormalities of glucose metabolism and the metabolic syndrome, including excess bodyweight, are potentially modifiable risk factors for cardiac morbidity and mortality. This study aimed to determine the prevalence of these in a group of patients presenting for elective cardiac catheterization or percutaneous intervention. METHODS: Data were prospectively collected on 297 consecutive patients presenting for elective cardiac catheterization or percutaneous intervention at a single tertiary referral centre. Demographic data, risk factors, medications and coronary angiogram results were recorded. Fasting lipids, fasting glucose, HbA1c levels were measured and if necessary an oral glucose tolerance test was carried out. Logistic regression and contingency table analysis examined associations of these with ethnicity. RESULTS: Impaired glucose metabolism (diabetes, impaired glucose tolerance or impaired fasting glucose) was present in 46.1% with our screening programme detecting previously unknown impaired glucose metabolism in 22.9%. Impaired glucose metabolism was strongly associated with non-European ethnicity (P < 0.0001). The metabolic syndrome was present in 49.2%. When defined by ethnic specific cut-offs, overweight or obesity was present in >80% of patients in all ethnic groups. CONCLUSION: There is a very high prevalence of impaired glucose metabolism and the metabolic syndrome in patients presenting for cardiac catheterization. Impaired glucose metabolism is particularly prevalent in the Polynesian and the Indian and the Sri Lankan ethnic groups. Screening of patients undergoing elective cardiac catheterization identifies a significant number of patients with undiagnosed impaired glucose metabolism and should be carried out routinely.

A simplified approach to temporary DDD pacing using a single lead, balloon-tipped catheter with overlapping biphasic impulse stimulation.

Temporary DDD pacing offers significant hemodynamic benefits in emergency management of bradyarrhythmias but is underused because of its complexity (two leads) and unreliability. Single lead VDD pacing with atrial sensing via a floating dipole is feasible, but atrial pacing is limited by high thresholds and phrenic nerve stimulation (PNS). Overlapping biphasic impulse (OLBI) stimulation may avoid these problems. The authors designed a single lead balloon-tipped catheter for temporary transvenous DDD pacing, incorporating noncontact atrial dipoles for OLBI stimulation. This catheter was deployed using fluoroscopic guidance in 74 patients (43 men, 31 women) with mean age 56.9 +/- 17.0 years. Pacing parameters were assessed at implantation and follow-up. The median procedural time was 6.6 (range 1.2-25.0) minutes and fluoroscopy time 1.9 (range 0.2-7.8) minutes. Stable VDD pacing was achieved in all cases. Atrial capture was achieved in 73 of 74 cases with both modes at maximum output but was restricted by PNS at outputs below atrial capture threshold in 3 of 74 cases with OLBI and 10 of 74 cases with standard bipolar mode (P = 0.04). At outputs > or = 1.0 V above atrial threshold, reliable DDD pacing without PNS was achieved and maintained in 67 (91%) of 74 patients in OLBI compared to 53 (72%) of 74 patients in bipolar mode (P = 0.003). Pacing parameters were stable during follow-up (median 53 hours, range 6-168 hours). In conclusion, the single lead catheter with OLBI stimulation allows temporary VDD and DDD pacing without PNS to be achieved in > 90% of patients. This rapid and convenient approach should facilitate DDD pacing in emergency settings.

Treatment of hypothyroidism with once weekly thyroxine.

We compared daily T4 therapy with 7 times the normal daily dose administered once weekly in 12 hypothyroid subjects in a randomized cross-over trial. At the end of each treatment we measured serum free T4 (FT4), free T3 (FT3), rT3, and TSH levels and multiple markers of thyroid hormone effects at the tissue level repeatedly for 24 h. Compared with daily administration, the mean serum TSH before the administration of weekly T4 was higher (weekly, 6.61; daily, 3.92 microIU/mL; P < 0.0001), and the mean FT4 (weekly, 0.98; daily, 1.35 ng/dL; P < 0.01) and FT3 (weekly, 208, daily, 242 pg/dL; P < 0.01) were lower. A minimally elevated serum total cholesterol during weekly administration (weekly, 246.8; daily, 232.6 mg/dL; P < 0.03) was the only evidence of hypothyroidism at the tissue level. Compared with daily administration, the mean peak FT4 following weekly administration of T4 was significantly higher (weekly, 2.71; daily, 1.59 ng/dL; P < 0.0001), as was the mean peak FT3 level (weekly, 285; daily, 246 pg/dL; P < 0.01). None of the tissue markers of thyroid hormone effect changed compared to daily T4, and there was no evidence of treatment toxicity, including cardiac toxicity. During weekly T4 administration, autoregulatory mechanisms maintain near-euthyroidism. For complete biochemical euthyroidism a slightly larger dose than 7 times the normal daily dose may be required.

Serial MRI in listeria mesenrhombencephalitis: a case report.

Listeria mesenrhombencephalitis is a rare disorder, especially in the non-immunocompromised host. The predilection for brain stem involvement is unexplained. The anatomical correlation of brain stem signs with serial MRI over three months is shown in a 64 year old white man. The pathological lesions seemed to be a combination of micro-abscesses and associated oedema.

[Values of certain prosodic parameters obtain with French-speaking probands without communication problems]. / Valeurs de certains paramètres prosodiques obtenues auprès de sujets francophones sans trouble de la communication.

Acoustic data are provided in order to facilitate evaluation of the speech of adult patients with prosody disorders such as dysarthria. Forty French-speaking subjects between 45 and 75 years of age, with neither neurological disease nor a communication disorder, were grouped on the basis of sex and age. Subjects were required to produce four series of 20 matched interrogative and declarative sentences. Their productions were recorded and analyzed with an IBM Speech Viewer. Measures of fundamental frequency, of variation in fundamental frequency, of rate over the entire sentence, as well as a measure of intonation (defined as the difference in fundamental frequency between the last syllable of matched declarative and interrogative sentences) are reported in tables for clinical use. These data provide information for the evaluation of the prosody of French-speaking persons.