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.

Prasugrel inhibits platelet-enhanced pro-inflammatory CD4+ T cell responses in humans.

While platelets have well characterized effects on monocytes, the effect of platelet activation on CD4+ T-cell differentiation and cytokine production is not clear. To examine the effects of platelet T-cell interactions on T-cell phenotype, and whether these interactions were altered by prasugrel, we conducted a randomized, double-blind, placebo-controlled crossover study in healthy subjects. At baseline the addition of platelets to CD4+ T-cells resulted in an increase in the release of pro-inflammatory cytokine IFN-γ (192% increase in IFN-γ levels, p = 0.01) and pro-inflammatory CD4+ phenotypes, (38% and 58% increase in Th1 and Th17 phenotypic markers respectively, p = 0.01) but no change in Tregs. Prasugrel abolished the effects of platelets on CD4+ T-cells with similar levels of pro-inflammatory cytokines and cell numbers to T-cells stimulated. Antiplatelet therapy may provide therapeutic benefit both from direct platelet inhibition and also through indirect effects on immune response development.

Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population.

BACKGROUND: High on-treatment platelet reactivity has been associated with poor outcomes following acute coronary syndromes (ACS). Both the loss of function CYP2C19*2 allele and the gain of function CYP2C19*17 allele along with a range of clinical characteristics have been associated with variation in the response to clopidogrel. AIM: The study aims to examine the frequency of CYP2C19 variants and understand the factors associated with on-treatment platelet reactivity in a New Zealand ACS population. METHODS: We prospectively enrolled 312 ACS patients. We collected clinical characteristics and measured on-treatment platelet reactivity using two validated point-of-care assays, VerifyNow and Multiplate. DNA was extracted and CYP2C19*2 and *17 alleles were identified using real-time polymerase chain reaction. RESULTS: CYP2C19*2 or CYP2C19*17 alleles were observed in 101 (32%) and 106 (34%) of patients, respectively, with significant differences in distribution by ethnicity. In Maori and Pacific Island patients, 47% (confidence interval (CI) 31-63%) had CYP2C19*2 and 11% (CI 4-19%) CYP2C19*17 compared with 26% (CI 19-32%) and 41% (CI 32-49%) in white people. Carriage of CYP2C19*2 alleles was associated with higher levels of platelet reactivity measured by either assay, but we observed no relationship between platelet reactivity and CYP2C19*17. In multivariate analysis diabetes, clopidogrel dose and CYP2C19*2 status were all significant independent predictors of platelet reactivity. CONCLUSIONS: Both CYP2C19*2 and *17 were common in a New Zealand ACS population, with CYP2C19*2 observed in almost half the Maori and Pacific Island patients. CYP2C19*2, diabetes and clopidogrel dose were independent contributors to on-treatment platelet reactivity.

Suboptimal response to clopidogrel and the effect of prasugrel in acute coronary syndromes.

BACKGROUND: High on clopidogrel platelet reactivity (HPR) has been associated with adverse outcomes following acute coronary syndromes (ACS). This study investigated the rate of HPR in a New Zealand ACS population and examined the effectiveness of prasugrel in reducing platelet reactivity in those with HPR. METHODS: In this prospective cohort study, 250 patients with ACS were pretreated with aspirin and clopidogrel and residual platelet reactivity was measured using whole blood multiple electrode platelet aggregometry. Twenty-seven of the patients with HPR were treated with prasugrel at the discretion of their physician, and platelet reactivity retested. RESULTS: Ninety-five patients (38%) had HPR. Maori and Pacific Island patients had a higher rate of HPR compared to Europeans (57% versus 35.9%, p=0.013). Additionally, patients with diabetes were also found to have higher rate of HPR compared to non-diabetics (50% versus 34.8%, p=0.045). Patients treated with a low dose clopidogrel regimen had significantly higher rates of HPR (45.4%) compared to those treated with intermediate (25.4%) or high dose regimens (26.8%, p=0.009). All of the 27 patients with HPR who were subsequently treated with prasugrel (60 mg) had a significant decrease in platelet reactivity (660 AU min (565-770) before versus 230 AU min (110-345) after, p<0.001), and was reduced to below the HPR cutoff in 24 (88.9%) of the patients. CONCLUSIONS: Ethnicity, diabetes and clopidogrel dose contributed to HPR. The use of prasugrel in those with HPR resulted in a consistent and marked reduction in platelet reactivity.

Cardioventilatory coupling and inter-breath variability in children referred for polysomnography.

Measures of respiratory variability including cardioventilatory coupling (CVC), were examined in 8 Down syndrome (DS), 4 Prader Willi syndrome (PWS) and 42 non-syndromic children (median age 7 years) referred for diagnostic polysomnography. Inspiratory onsets (I) and corresponding ECG R waves were determined, I-I, R-R and R-I intervals derived, and ventilatory frequency (f), standard deviation of f (SDf), coefficient of variation of f (CVf), median I-I and kurtosis and skewness I-I calculated. Proportional Shannon Entropy of the RI(-1) interval (SHα) was measured to quantitate CVC. SHα varied with age (p=0.02), oxygen saturation (p<0.05) and PWS diagnosis (p=0.001) in Stage 4 but not REM sleep. SDf and CVf varied with sleep state (p<0.00001) as did kurtosis I-I (p<0.0001) and skewness I-I (p=0.004). Ventilatory frequency decreased with age in REM sleep (p=0.03) and increased in obese children in REM (p=0.02) and Stage 4 sleep (p=0.004). Sleep state influences respiratory variability in children and CVC may confer a physiological advantage in children with PWS.

Respiratory sinus arrhythmia in conscious humans during spontaneous respiration.

Respiratory sinus arrhythmia (RSA) is the beat-to-beat fluctuation in heart rate at the frequency of the respiratory cycle. While it is common to study RSA under conditions of controlled breathing, where respiratory frequency, and sometimes tidal volume and inspiratory:expiratory ratio are controlled, the effect of controlled breathing on RSA is not clear. While not all studies exploring the effects of controlled breathing on RSA magnitude are consistent, some of the best-designed studies addressing this question did find a significant effect. In addition to respiratory timing influencing heartbeats, there is evidence that cardiac timing also influences respiratory timing, termed cardioventilatory coupling. Thus, the timing interactions between the cardiac and respiratory systems are complex, and bi-directional. Controlled breathing eliminates one aspect of this relationship, and studies designed to understand cardiorespiratory physiology conducted under these conditions need to be interpreted with an understanding that they may not represent normal physiology.

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.

Effects of hypercapnia and hypoxemia on respiratory sinus arrhythmia in conscious humans during spontaneous respiration.

Normally, at rest, the amplitude of respiratory sinus arrhythmia (RSA) appears to correlate with cardiac vagal tone. However, recent studies showed that, under stress, RSA dissociates from vagal tone, indicating that separate mechanisms might regulate phasic and tonic vagal activity. This dissociation has been linked to the hypothesis that RSA improves pulmonary gas exchange through preferential distribution of heartbeats in inspiration. We examined the effects of hypercapnia and mild hypoxemia on RSA-vagal dissociation in relation to heartbeat distribution throughout the respiratory cycle in 12 volunteers. We found that hypercapnia, but not hypoxemia, was associated with significant increases in heart rate (HR), tidal volume, and RSA amplitude. The RSA amplitude increase remained statistically significant after adjustment for respiratory rate, tidal volume, and HR. Moreover, the RSA amplitude increase was associated with a paradoxical rise in HR and decrease in low-frequency-to-high-frequency mean amplitude ratio derived from spectral analysis, which is consistent with RSA-vagal dissociation. Although hypercapnia was associated with a significant increase in the percentage of heartbeats during inspiration, this association was largely secondary to increases in the inspiratory period-to-respiratory period ratio, rather than RSA amplitude. Additional model analyses of RSA were consistent with the experimental data. Heartbeat distribution did not change during hypoxemia. These results support the concept of RSA-vagal dissociation during hypercapnia; however, the putative role of RSA in optimizing pulmonary perfusion matching requires further experimental validation.

Mechanism of cardioventilatory coupling: insights from cardiac pacing, vagotomy, and sinoaortic denervation in the anesthetized rat.

Cardioventilatory coupling (CVC), a temporal alignment between the heartbeat and inspiratory activity, is a major determinant of breath-to-breath variation in observed respiratory rate (f(o)). The cardiac-trigger hypothesis attributes this to adjustments of respiratory timing by baroreceptor afferent impulses to the central respiratory pattern generator. A mathematical model of this hypothesis indicates that apparent CVC in graphical plots of ECG R wave vs. inspiratory time is dependent on the heart rate (HR), the rate of the intrinsic respiratory oscillator (f(i)), and the strength of the hypothetical cardiovascular afferent impulse. Failure to account for HR and f(i) may explain the inconsistent results from previous attempts to identify the neural pathways involved in CVC. Cognizant of these interactions, we factored in the HR-to-f(i) ratio in our examination of the role of the vagus nerve and arterial baroreceptors in CVC by cardiac pacing 29 anesthetized Sprague-Dawley rats and incrementally changing the HR. With the assumption of a relatively constant f(i), CVC could be examined across a range of HR-to-f(o) ratios before and after vagotomy, sinoaortic denervation, and vagotomy + sinoaortic denervation. We confirmed the relation between CVC, HR-to-f(o) ratio, and breath-to-breath respiratory period variability and demonstrated the loss of these relations after baroreceptor elimination. Sham experiments (n = 8) showed that these changes were not due to surgical stress. Our data support the notion that inspiratory timing can be influenced by cardiac afferent activity. We conclude that the putative cardiovascular input arises from the arterial baroreceptors and that the vagus nerve is not critical for CVC.

Knowledge of and attitudes towards resuscitation in New Zealand high-school students.

BACKGROUND: Introducing cardiopulmonary resuscitation (CPR) training in the high-school curriculum has been widely recommended as a long-term strategy to educate the wider community. Although CPR has been included in the New Zealand school curriculum, it is listed as an optional subject only. AIM: To assess the attitude towards and knowledge of CPR in 16-17-year-old high-school students in New Zealand. METHODS: Questionnaires were administered to 494 students aged 16-17 years across six high schools in Wellington, New Zealand. Both knowledge and attitude were evaluated in the questionnaire. RESULTS: Students showed poor theoretical knowledge, with a mean (SD) score of 5.61 (2.61) out of a maximum score of 18. Although there was no difference between male and female students, those who had received previous first-aid training (70%) showed greater knowledge (6.04 (2.56)) than their untrained counterparts (4.91 (2.24); p = 0.001). Those students with a positive attitude towards CPR and first-aid training (63%) acquired a higher knowledge score (6.12 (2.4)) than those with a negative attitude (17%; 4.65 (2.5); p = 0.001). Students with negative associations were also less likely to want to learn more about CPR and first aid (11%) when compared with those with positive associations (92%), and indicated less willingness to perform CPR on a stranger (negative v positive, 47% v 70%). CONCLUSIONS: These findings suggest that although most high-school students are willing and motivated to learn CPR, a smaller percentage of students had a negative attitude towards CPR that would act as a barrier to future learning or performance of resuscitation. Introducing CPR training to high schools is still recommended; however, this study shows the need to associate this training with positive references in an attempt to assist those for whom negative attitude may present as a barrier to learning and retaining CPR knowledge.

The sound of silence is music to the heart.

The underlying tempo of different types of music may have an effect on heart rate and blood pressure.

Quantal breathing frequency variation in halothane anaesthetised neonatal rats.

We examined the changes in cardioventilatory synchronisation and breathing frequency variability that occur during early postnatal development in anaesthetised rats. Five-minute periods of heart rate and inspiratory timing data were recorded from 26 halothane anaesthetised, spontaneously breathing rats aged 2-14 days. The presence of cardioventilatory synchronisation was determined by examining the timing relationship between inspiratory onset and the preceding ECG R waves. We observed synchronisation at all ages, and the degree of synchronisation present (measured as the Shannon entropy of the interval between inspiration and the immediately preceding R wave) did not correlate with age. Frequent apnoeas were observed in the respiratory frequency time series. The duration of these apnoeas was close to either one or two times the duration of the immediately preceding breath. We suggest that these "dropped breaths" may be the consequence of a resetting of the respiratory oscillator just prior to initiation of the breath, or a gating process beneath the oscillator that intermittently blocks the mechanical initiation of breaths. Dropped breaths were seen commonly in rats up to 11 days of age, but rarely in 11-14-day old rats, and were not associated with the presence or absence of cardioventilatory synchronisation.

Psychometric characteristics of simulation-based assessment in anaesthesia and accuracy of self-assessed scores.

The purpose of this study was to define the psychometric properties of a simulation-based assessment of anaesthetists. Twenty-one anaesthetic trainees took part in three highly standardised simulations of anaesthetic emergencies. Scenarios were videotaped and rated independently by four judges. Trainees also assessed their own performance in the simulations. Results were analysed using generalisability theory to determine the influence of subject, case and judge on the variance in judges' scores and to determine the number of cases and judges required to produce a reliable result. Self-assessed scores were compared to the mean score of the judges. The results suggest that 12-15 cases are required to rank trainees reliably on their ability to manage simulated crises. Greater reliability is gained by increasing the number of cases than by increasing the number of judges. There was modest but significant correlation between self-assessed scores and external assessors' scores (rho = 0.321; p = 0.01). At the lower levels of performance, trainees consistently overrated their performance compared to those performing at higher levels (p = 0.0001).

Effect of automatic external defibrillator audio prompts on cardiopulmonary resuscitation performance.

OBJECTIVES: To determine the effectiveness of the cardiopulmonary resuscitation (CPR) audio prompts in an automatic external defibrillator in 24 lay subjects, before and after CPR training. METHODS: Untrained subjects were asked to perform CPR on a manikin with and without the assistance of audio prompts. All subjects were then trained in CPR, and retested them eight weeks later. RESULTS: Untrained subjects who performed CPR first without audio prompts performed poorly, with only (mean (SD)) 24.5% (32%) of compressions at the correct site and depth, a mean compression rate of 52 (31) per minute, and with 15% (32%) of ventilatory attempts adequate. Repeat performance by this group with audio prompts resulted in significant improvements in compression rate (91(12), p = 0.0002, paired t test), and percentage of correct ventilations (47% (40%), p = 0.01 paired t test), but not in the percentage correct compressions (23% (29%)). Those who performed CPR first with audio prompts performed significantly better in compression rate (87 (19), p = 003, unpaired t test), and the percentage of correct ventilations (51 (34), p = 0.003 unpaired t test), but not in the percentage of correct compressions (18 (27)) than those without audio prompts. After training, CPR performance was significantly better than before training, but there was no difference in performance with or without audio prompts, although 73% of subjects commented that they felt more comfortable performing CPR with audio prompts. CONCLUSIONS: For untrained subjects, the quality of CPR may be improved by using this device, while for trained subjects the willingness to perform CPR may be increased.

Fractal characteristics of breath to breath timing in sleeping infants.

We examined interbreath interval (IBI) time series of 19 term infants during active and quiet sleep for fractal properties using Fano factor analysis. For each time series we calculated the fractal exponent (alpha), comparing alpha for the original time series with two forms of surrogate data, a temporally independent surrogate set and an autoregressive surrogate set. alpha values were normally distributed between 0.79 and -0.22, and did not differ with sleep state. The fractal characteristics of the original time series were not retained in the temporally independent surrogate time series indicating that the distribution of intervals alone was not fractal, but were retained using autoregressive surrogates with an order of 10, suggesting that the fractal properties of the IBI time series were related to correlations between successive breaths. These observations suggest that some of the respiratory variability that occurs during sleep in infants, which in the past has been regarded as stochastic noise, may be the product of deterministic processes.

Inspiratory coupling to cardiac activity and to somatic afferent nerve stimulation in the anaesthetised rat.

We examined the ability of somatic afferent nerve stimulation to entrain inspiratory onset in the anaesthetized spontaneously breathing rat, and compared features of this stimulus-ventilatory coupling to entrainment of inspiratory onset by cardiac activity. In 14 rats prior to stimulation, we commonly observed a constant temporal alignment between ECG R waves and inspiratory onset (cardioventilatory coupling). Stimulation of a hamstring nerve at rates close to the heart rate also caused coupling (a constant stimulus to inspiratory onset interval), although this was highly dependent upon frequency of stimulation, with small changes in frequency causing a loss of coupling. In experiments where stimuli were given at constant intervals after ECG R waves, we observed no augmentation of coupling. Our results indicate that both cardiac and somatic afferent nerve activity is able to entrain inspiratory onset. We have suggested that coupling causes respiratory frequency to increase, and it is possible that this is a general mechanism whereby non-respiratory afferents act as stimulants or pacemakers to respiratory rhythm. The role of non-respiratory activity in initiating inspiration needs to be more fully recognised and studied.

Cardioventilatory coupling in resting human subjects.

In 48 conscious resting subjects we examined the temporal coupling of heart beat timing and the onset of inspiration (cardioventilatory coupling), and the relationship between coupling and spectral indices of autonomic function. Using the proportional Shannon entropy (SH(alpha)) of the RI(-1) interval (interval between inspiration and the preceding ECG R wave) as a measure of coupling we detected statistically significant coupling in 32 of the 48 subjects. This was confirmed by visual inspection of time series plots of RI intervals, in which coupling was evident as horizontal banding. Coupling resulted in a significant preference for whole number heart rate/respiratory frequency ratios. The strongest coupling was associated with low ventilatory frequency and high heart rate variability in the high (0.15-0.40 Hz) and low (0.04-0.15 Hz) frequency ranges, but was not related to blood pressure variability, or to a spectral measure of baroreflex sensitivity (alpha-index, low frequency range). There was no difference in coupling strength between males and females. We have previously described cardioventilatory coupling in spontaneously breathing anaesthetised subjects. The current study extends those observations by demonstrating that the qualitative features of coupling seen during anaesthesia are also observed in the conscious state. We conclude that the role of coupling in normal physiological respiratory control needs to be more widely explored.

Quantal ventilatory variability during spontaneous breathing anaesthesia.

BACKGROUND: Cardioventilatory coupling is the triggering of inspiratory onset by preceding cardiac activity. We have observed two forms of coupling with a bimodal ('quantal') variation of respiratory period. METHODS: We investigated the variables of inspiratory duration (TI), expiratory duration (TE), and tidal volume (VT) where respiratory period variation was bimodal. In 25 anaesthetized spontaneously breathing subjects we took 11 samples of recording where the variation of respiratory period was quantal. RESULTS: In eight of these epochs the variation in respiratory period was associated with fluctuations in the number of heart beats per breath (entrainment ratio) with a constant time interval between inspiration and the immediately preceding heart beat (coupling interval), which we define as pattern II coupling. During pattern II coupling, the quantal variations in respiratory period were entirely caused by variation in TE, with no associated changes in either TI or VT. The other three epochs with quantal variations in respiratory period were observed in pattern III coupling, where an alternating fluctuation in both entrainment ratio and coupling interval occurs. During pattern III coupling, quantal fluctuations were observed in TE, TI, and VT. IMPLICATIONS: Cross correlation analysis suggested that when pattern III was present, TI was dependent upon the preceding TE, which differs markedly from traditional views on the interaction between inspiratory and expiratory duration. VT was linearly related to TI, and so could also be determined by the preceding TE during this type of coupling.

Comparison of ease of use of three automated external defibrillators by untrained lay people.

The use of automated external defibrillators (AED) by lay people has the potential to markedly increase survival from community cardiac arrest. Wider public use of AEDs requires units that can be operated safely and effectively by people with minimal or no training. This study compares the use of three AEDs by untrained lay people regarding ease-of-use, safety, pad positioning and time to defibrillation. 24 subjects with no prior exposure to the use of AEDs were asked to perform simulated defibrillation on a manikin using three defibrillators: Zoll AEDPlus, Medtronic Physio-Control LifePak CR Plus and Philips/Laerdal HeartStart OnSite Defibrillator. Subjects' performance were videotaped and reviewed for time to defibrillate, pad positioning and safety. Subjects were asked to rate the three units in terms of ease-of-use. Average times to first shock were 74.8 s for the Physio-Control, 83.0 s for the Laerdal and 153.4 s for the Zoll defibrillator. Pad positioning was scored as correct in 23/24 Laerdal trials, 19/24 Physio-Control trials and 14/24 Zoll trials. 23 out of the 24 subjects rated the Zoll most difficult to use. All subjects safely stayed clear of the unit when required. The majority of subjects safely and effectively delivered defibrillating shocks without any prior training and within quite acceptable times. Untrained subjects find the Physio-Control and Laerdal Defibrillator easier to use than the Zoll device. Features of AED design that improved ease of use are discussed.

Comparison of heart rate variability in supine, and left and right lateral positions.

In order to determine whether differences exist in cardiac autonomic tone between different body positions that may be used in unconscious subjects, we examined beat-to-beat heart rate variability (HRV) in volunteers lying supine, and in left lateral and right lateral positions. We studied 24 subjects, aged 20-35 years in each of the three positions on one study day, and 6 subjects in each of the three positions on each of six different study days. In both groups of subjects we observed no difference in heart rate, respiratory frequency, total power (0.02-0.45 Hz) of HRV or the proportion of power in the high (0.15-0.45 Hz), low (0.08-0.15 Hz) or very low (0.02-0.08 Hz) frequency bands among the three positions. These results suggest that there are no cardiac autonomic tone advantages to be gained by placing a person in the recovery position on one side compared with the other.