State of the art: leadless ventricular pacing : A national expert consensus of the Austrian Society of Cardiology.

BACKGROUND: Cardiac pacing has been shown to improve quality of life and prognosis of patients with bradycardia for almost 60 years. The latest innovation in pacemaker therapy was miniaturization of generators to allow leadless pacing directly in the right ventricle. There is a long history and extensive experience of leadless ventricular pacing in Austria. However, no recommendations of national or international societies for indications and implantation of leadless opposed to transvenous pacing systems have been published so far. RESULTS: A national expert panel of skilled implanters gives an overview on the two utilized leadless cardiac pacing systems and highlights clinical advantages as well as current knowledge of performance and complication rates of leadless pacing. Furthermore, a national consensus for Austria is presented, based on recent studies and current know-how, specifically including indications for leadless pacing, management of infection, suggestions for qualification, and training of the operators and technical standards. CONCLUSIONS: Leadless pacing systems can be implanted successfully with a low complication rate, if suggestions for indications and technical requirements are followed. An overview of the two utilized leadless cardiac pacing systems is given, specifically highlighting clinical advantages as well as current knowledge of performance and complication rates. Furthermore, a national consensus for Austria is presented, specifically including indications for leadless pacing, management of infection, and suggestions for qualification and technical standards.

Socio-economic effects and cost saving potential of remote patient monitoring (SAVE-HM trial).

OBJECTIVE: In the SAVE-trial we evaluated the safety, reliability and improvements of patient management using the BIOTRONIK Home Monitoring®-System (HM) in pacemaker (PM) and implanted cardioverter defibrillator (ICD) patients. DESIGN: 115 PM (Module A) and 36 ICD-patients (Module B) were recruited 3 months after implantation. PATIENTS: 65 patients in Module A were randomised to HM-OFF and had one scheduled outpatient clinic follow-up(FU) per year, whereas patients randomised to HM-ON were equipped with the mobile transmitter and discharged without any further scheduled in-office FU. In Module B 18 patients were randomised to HM-OFF and followed by standard outpatient clinic controls every 6 months; 18 patients were randomised to HM-ON receiving remote monitoring plus one outpatient clinic visit per year; unscheduled follow-ups were performed when necessary. RESULTS: The average follow-up period was 17.1 ± 9.2 months in Module A and 26.3 ± 8.6 months in Module B. In both modules, the number of FUs per year was significantly reduced (Module A HM-ON 0.29 ± 0.6 FUs/year vs HM-OFF 0.53 ± 0.5 FUs/year; p b 0.001; Module B HM-ON 0.87 ± 0.25 vs HM-OFF 1.73 ± 0.53 FU/year,p b 0.001). Cost analysis was significantly lower in the HM-ON group compared to the HM-OFF group (18.0 ± 41.3 and 22.4 ± 26.9 € respectively; p b 0.003). 93% of the unscheduled visits in Module B were clinically indicated,whereas 55% of the routine FUs were classified as clinically unnecessary. CONCLUSION: Remote home monitoring of pacemaker and ICD devices was safe, reduced overall hospital visits, and detected events that mandated unscheduled visits.

The effects of railway noise on sleep medication intake: results from the ALPNAP-study.

In the 1980s/90s, a number of socio-acoustic surveys and laboratory studies on railway noise effects have observed less reported disturbance/interference with sleep at the same exposure level compared with other modes of transportation. This lower grade of disturbance has received the label "railway bonus", was implemented in noise legislation in a number of European countries and was applied in planning and environmental impact assessments. However, majority of the studies investigating physiological outcomes did not find the bespoke difference. In a telephone survey (N=1643) we investigated the relationship between railway noise and sleep medication intake and the impact of railway noise events on motility parameters during night was assessed with contact-free high resolution actimetry devices. Multiple logistic regression analysis with cubic splines was applied to assess the probability of sleep medication use based on railway sound level and nine covariates. The non-linear exposure-response curve showed a statistically significant leveling off around 60 dB (A), Lden. Age, health status and trauma history were the most important covariates. The results were supported also by a similar analysis based on the indicator "night time noise annoyance". No railway bonus could be observed above 55 dB(A), Lden. In the actimetry study, the slope of rise of train noise events proved to be almost as important a predictor for motility reactions as was the maximum sound pressure level - an observation which confirms similar findings from laboratory experiments and field studies on aircraft noise and sleep disturbance. Legislation using a railway bonus will underestimate the noise impact by about 10 dB (A), Lden under the conditions comparable with those in the survey study. The choice of the noise calculation method may influence the threshold for guideline setting.

Comparison of measurements and predictions of sound propagation in a valley-slope configuration in an inhomogeneous atmosphere.

Mountainous areas form a very specific context for sound propagation: There is a particular ground effect and meteorological conditions are often extreme. In this paper, detailed sound propagation calculations are compared to noise measurements accompanied by meteorological observations. The sound source considered is road traffic along the center axis of a valley. Noise levels were measured in two cross sections, at three locations each: one on the valley floor and two on the slopes, up to 166 m above the source. For the numerical calculations, the rotated Green's function parabolic equation method is used, taking into account the undulation of the terrain and an inhomogeneous atmosphere. Typical parameters of this method were optimized for computational efficiency. Predictions agree with measurements to within 3 dBA up to propagation distances of 1 km, in windless conditions. The calculations further show that the terrain profile is responsible for an increase in sound pressure level at distant, elevated points up to 30 dBA compared to a flat ground situation. Complex temperature profiles account for level changes between -3 dBA and +10 dBA relative to a homogeneous atmosphere. This study shows that accurate sound level prediction in a valley-slope configuration requires detailed numerical calculations.

Automated and manufacturer independent assessment of the battery status of implanted cardiac pacemakers by electrocardiogram analysis.

According to international standards, cardiac pacemakers have to indicate the status of their batteries upon magnet application by specific stimulation patterns. The purpose of this study has been to assess whether this concept can be used as a basis for automated and manufacturer independent examination of the depletion level of pacemakers in the framework of a collaborative telemedical pacemaker follow-up system. A prototype of such a system was developed and tested in a real clinical environment. Electrocardiograms (ECGs) were recorded during magnet application and automatically processed to extract the specific stimulation patterns. The results were used to assign each signal a corresponding pacemaker status: "ok," "replace" or "undefined," based on the expected behavior of the devices as specified by the manufacturer. The outcome of this procedure was compared to the result of an expert examination, resulting in a positive predictive value of 100% for the detection of ECGs indicating pacemaker status "ok." The method can, therefore, be utilized to quickly, safely and manufacturer neutrally classify cases into the categories "ok" and "needs further checking," which - in a telemedical setting - may be used to increase the efficiency of pacemaker follow-up procedures in the future.

Aborted sudden death in a patient with a structurally normal heart: the Brugada syndrome.

We report a 37-year-old man with documented aborted sudden death. After resuscitation, the patient showed no structural heart disease but the ECG showed a right bundle-branch block with a descending ST segment elevation in leads V(1) and V(2). After transient normalization of the ECG, the administration of ajmaline led to spontaneous development of the distinct descending ST segment elevation in the right precordial leads and therefore to the diagnosis of Brugada syndrome. The incidence of sudden cardiac death among these patients is high. The only treatment is an implantable cardioverter-defibrillator (ICD). The Brugada syndrome should therefore be borne in mind in the differential diagnosis of sudden death.

Ambient neighbourhood noise and children's mental health.

OBJECTIVES: To investigate the relation between typical ambient noise levels (highway, rail, road) and multiple mental health indices of school children considering psychosocial and biological risk factors as potential moderators. METHODS: With a two stage design strategy (representative sample and extreme sample) two cross sectional samples (n=1280; n=123) of primary school children (age 8-11) were studied. Individual exposure to noise at home was linked with two indices of mental health (self reporting by the child on a standard scale and rating by the teacher of classroom adjustment on a standard scale). Noise exposure was modelled firstly according to Austrian guidelines with the aid of a geographical information system and then calibrated and corrected against measurements from 31 locations. Information on potential confounders and risk factors was collected by mothers and controlled in regression modelling through a hierarchical forward stepping procedure. Interaction terms were also analysed to examine subgroups of children at risk-for example, low birth weight and preterm birth. RESULTS: Noise exposure was significantly associated in both samples with classroom adjustment ratings. Child self reported mental health was significantly linked to ambient noise only in children with a history of early biological risk (low birth weight and preterm birth). CONCLUSIONS: Exposure to ambient noise was associated with small decrements in children's mental health and poorer classroom behaviour. The correlation between mental health and ambient noise is larger in children with early biological risk.

Noise Annoyance Modelling using Fuzzy Rule Based Systems.

This paper presents a model that uses a fuzzy rule based engine to predict noise annoyance reported by individuals in a social survey. The rules are proposed by the human expert and are based on linguistic variables. The approach then adapts the sufficiency degree or certainty of a rule to tune the model to a particular survey. Although all possible relations between exposure, attitudinal, emotional, personal, environmental and social variables are not included in the model as yet, the benefits of the new approach are clearly demonstrated. A major limitation that remains is the varying theoretical and empirical basis of the expert for different subset of annoyance determinants. Future applications may include more accurate predictions of noise annoyance for policy support and extraction of knowledge concerning the construct of annoyance from surveys.

Differential effects of growth hormone therapy in malnourished hemodialysis patients.

BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is associated with increased morbidity and mortality. Several factors such as metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth hormone (rhGH) has been proposed as treatment of malnutrition because of its anabolic effects. METHODS: In the present placebo-controlled, double blind study, the effects of three months of rhGH therapy on nutritional and anthropometric parameters, on bone metabolism and bone mineral density (BMD), as well as on polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a week during the first four weeks and 0.25 IU/kg thereafter three times a week after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I) concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4 ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin, cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase, predialytic creatinine, and blood urea nitrogen showed no significant changes during the three months in both groups. Total body fat (%TBF) was slightly reduced after three months (P = NS) in the patients receiving GH, whereas lean body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal peptide (PICP), a marker of bone formation, increased significantly after three months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH-treated patients, whereas parameters of bone resorption like telopeptide ICTP showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS). BMD at the lumbar spine decreased significantly after three months in the treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at the femoral neck remained stable in both groups. Phagocytic activity of PMNLs increased significantly after three months of therapy with rhGH, whereas other parameters of PMNL function were not affected by GH. QoL was slightly improved in the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS: Three months of treatment with rhGH in malnourished patients on chronic hemodialysis causes a significant increase in IGF-I levels without significant changes in nutritional and anthropometric parameters. In contrast, bone turnover was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic activity of PMNLs was increased.

Stereoselective effects of (R)- and (S)-carvedilol in humans.

Carvedilol is currently used as the racemic mixture, (R,S)-carvedilol, consisting of equal amounts of (R)-carvedilol, an alpha-blocker, and (S)-carvedilol, an alpha- and beta-blocker, which have never been tested in their optically pure forms in human subjects. We performed a randomized, double-blind, placebo-controlled, crossover study in 12 healthy male volunteers. Subjects received single oral doses of 25 mg (R,S)-carvedilol, 12.5 mg (R)-carvedilol, 12.5 mg (S)-carvedilol, and placebo at 8 AM as well as at 8 PM. Exercise was performed at 11 AM, and heart rate and blood pressure were measured at rest and after 10 min of exercise. Urine was collected between 10 AM and 6 PM, as well as between 10 PM and 6 AM, and the amounts of urinary 6-hydroxy-melatonin sulfate (aMT6s) were determined by RIA. Compared to placebo, (R)-carvedilol increased heart rate during exercise (+4%, P < 0.05) and recovery (+10%, P < 0.05); (S)-carvedilol decreased heart rate during exercise (-14%, P < 0.05) and recovery (-6%, P < 0.05), and systolic blood pressure during exercise (-12%, P < 0.05); (R,S)-carvedilol decreased heart rate during exercise (-11%, P < 0.05), and systolic blood pressure at rest (-7%, P < 0.05) and during exercise (-10%, P < 0.05). None of the agents had any significant effect on the release of aMT6s. Our results indicate that only (S)-carvedilol causes beta-blockade, whereas (R)-carvedilol appears to increase sympathetic tone, presumably as a physiological reaction to the decrease of blood pressure caused by alpha-blockade. None of the drugs had any influence on melatonin release. The weak clinical net effect of beta-blockade of (R,S)-carvedilol at rest might be one reason why this drug causes fewer side effects than other beta-blockers, such as a reduction of nocturnal melatonin release.

Community noise exposure and stress in children.

Although accumulating evidence over the past two decades points towards noise as an ambient stressor for children, all of the data emanate from studies in high-intensity, noise impact zones around airports or major roads. Extremely little is known about the nonauditory consequences of typical, day-to-day noise exposure among young children. The present study examined multimethodological indices of stress among children living under 50 dB or above 60 dB (A-weighted, day-night average sound levels) in small towns and villages in Austria. The major noise sources were local road and rail traffic. The two samples were comparable in parental education, housing characteristics, family size, marital status, and body mass index, and index of body fat. All of the children were prescreened for normal hearing acuity. Children in the noisier areas had elevated resting systolic blood pressure and 8-h, overnight urinary cortisol. The children from noisier neighborhoods also evidenced elevated heart rate reactivity to a discrete stressor (reading test) in the laboratory and rated themselves higher in perceived stress symptoms on a standardized index. Furthermore girls, but not boys, evidenced diminished motivation in a standardized behavioral protocol. All data except for the overnight urinary neuroendocrine indices were collected in the laboratory. The results are discussed in the context of prior airport noise and nonauditory health studies. More behavioral and health research is needed on children with typical, day-to-day noise exposure.

E 047/1: a new class III antiarrhythmic agent.

The efficacy, pharmacokinetics, safety, and tolerability of E 047/1, an amiodarone derivative, were evaluated in patients with acute supraventricular or ventricular arrhythmia. In an open, nonrandomized prospective multicenter trial, 20 patients were treated with three different i.v. dosage regimens of E 047/1. Arrhythmia termination indicated efficacy. Pharmacokinetics were determined by measurements of drug plasma levels. Safety was judged by changes of blood pressure, heart rate, ECG parameters, and appearance of adverse events. For local tolerability, effects at the site of infusion were assessed. In patients with atrial fibrillation and/or atrial flutter, drug plasma levels and prolongation of QT interval were correlated with efficacy. In 10 (50%) patients, therapeutic intervention with E 047/1 was successful. Drug plasma levels rapidly decreased within 1 h after administration. Blood pressure values and ECG parameters stayed constant during the observation period. Proarrhythmic effects were not observed. As adverse events, vertigo, vomiting, and nausea in three (15%) and hypotension in one (5%) patient, respectively, occurred in the high-dose bolus regimen only. At the site of infusion, no adverse effects were found. No dependency between drug plasma levels and arrhythmia termination was found. E 047/1 has proven to be efficient and safe in the treatment of arrhythmia. E 047/1 is characterized by rapid plasma elimination, absence of proarrhythmic or cardiodepressive effects, mild adverse events, and excellent local tolerability. For further investigation, we recommend a combined bolus- and weight-adapted infusion regimen.

A Review of Environmental Noise and Mental Health.

The question of whether environmental noise exposure causes mental ill-health is still largely unanswered. This paper reviews the studies of environmental and industrial noise and mental ill-health published between 1993 and 1998 and suggests possibilities for future research. Recent community based studies suggest high levels of environmental noise are associated with mental health symptoms such as depression and anxiety but not with impaired psychological functioning. Several studies find that self-reported noise sensitivity does not interact with noise exposure to lead to increased vulnerability to mental ill-health. Chronic aircraft noise exposure in children impairs quality of life but does not lead to depression or anxiety. Further research on environmental noise and mental health should be accompanied by more accurate and detailed measurement of noise exposure and consideration of the impact of other environmental stressors and careful measurement of confounding factors such as social class. Target study populations exposed to noise should be chosen to avoid those where noise exposure is likely to have led to noise sensitive individuals moving away from the area. There should also be greater use of standardised instruments to measure a wider range of mental health outcomes. Also other physiological outcomes such as hormonal measures could with benefit be measured simultaneously.

The principle of toxicopy and its integration into the administrative proceedings in Austria.

Toxicopy can be understood as an analogon to placebo but within any setting. Placebo is state-of-the-art since decades with relevant consequences: Only those effects may be considered as being pharmacon-specific, that go beyond non-pharmacological ("Placebo") effects. Placebo--theory is a limitation for the applicability of Morgans Canon (4), which is/was accepted within medicine like an axiom: When searching for the causes of disease physiological causes need to be ruled out, before other especially psychological etiologies can be taken into consideration. Toxicopy principle could be confirmed in different settings all over the world, in old and young, male and female, rich and poor and in different cultures. Therefore Morgans Cannon is falsified. Toxicopy principle is accepted as state-of-the-art and part of stand court rulings of the Austrian administrative tribunal. The plant law in Austria--and in Germany--provides for the protection of citizens against health hazards caused by plants, regardless of their etiologies. Therefore, non-toxicological threats must also be considered in plant approval proceedings in future.

Decreased melatonin synthesis in patients with coronary artery disease.

AIMS: Decreased night-time plasma levels of melatonin were recently reported in patients with coronary artery disease, and it was postulated that melatonin production may be impaired, due to a lack of synthesizing enzymes. However, since artefacts possibly influencing the release pattern were not taken into account, this interpretation was strongly criticized. We therefore carefully investigated night-time melatonin production in patients with coronary artery disease using an appropriate experimental approach. Furthermore, we examined the effect of beta-blockers, a frequently used drug in coronary artery disease therapy. METHODS AND RESULTS: Forty-eight male patients with angiographically documented severe coronary artery disease, 24 of them taking beta-blockers daily in therapeutic dosages, were included. Eighteen age-matched men, with no evidence of coronary sclerosis, served as controls. To determine melatonin production, 6-sulfatoxymelatonin (aMT6s) was measured radioimmunologically from overnight urine. Urinary aMT6s concentration was significantly decreased in patients, and beta-blocker treatment did not further suppress melatonin production. CONCLUSIONS: The data obtained using this investigative approach provide clearcut evidence that melatonin production in patients with coronary artery disease is decreased. Whether a decreased melatonin level may be a predisposing factor for coronary artery disease, or whether the occurrence of coronary artery disease decreases melatonin synthesis remains to be determined.

Influence of beta-blockers on melatonin release.

OBJECTIVE: Melatonin is a mediator in the establishment of the circadian rhythm of biological processes. It is produced in the pineal gland mainly during the night by stimulation of adrenergic beta1- and alpha1-receptors. Sleep disturbances are common side-effects of beta-blockers. The influence of specific beta-blockade as well as that of combined alpha-and beta-blockade on melatonin production has not been investigated in humans before. METHODS: We performed a randomized, double-blind, placebo-controlled, cross-over study in 15 healthy volunteers. Subjects received single oral doses of 40 mg (R)-propranolol, 40 mg (S)-propranolol, 50 mg (R)-atenolol, 50 mg (S)-atenolol, 25 mg (R,S)-carvedilol, 120 mg (R,S)-verapamil or placebo at 1800 hours. Urine was collected between 2200 hours and 0600 hours, and 6-sulfatoxy-melatonin (aMT6s), the main metabolite of melatonin which is almost completely eliminated in urine, was determined by radioimmunoassay (RIA). RESULTS: Mean nocturnal excretion of aMT6s in urine after intake of the drugs was as follows (in microg): placebo 26; (R)-propranolol 24 (-7%, NS); (S)-propranolol 5 (-80%, P < 0.001); (R)-atenolol 27 (+7%, NS); (S)-atenolol 4 (-86%, P < 0.01); (R,S)-carvedilol 23 (-10%, NS); (R,S)-verapamil 29 (+14%, NS). These data show that only the specifically beta-blocking (S)-enantiomers of propranolol and atenolol decrease the nocturnal production of melatonin whereas the non-beta-blocking (R)-enantiomers have no effect. Unexpectedly, (R,S)-carvedilol which inhibits both alpha- and beta-adrenoceptors does not decrease melatonin production. CONCLUSION: These findings indicate that beta-blockers decrease melatonin release via specific inhibition of adrenergic beta1-receptors. Since lower nocturnal melatonin levels might be the reason for sleep disturbances, further clinical studies should investigate whether or not oral administration of melatonin might avoid this well-known side-effect of beta-blockers. The reason why (R,S)-carvedilol does not influence melatonin production remains to be determined.

Birth weight, education, environment, and lung function at school age: a community study in an alpine area.

Our aim was to assess the effect of birth weight, gestational age, predispositions, education, housing and environmental factors on indices of lung function and to evaluate selective interactions among the main predictors. We studied schoolchildren (aged 7.5-12 yrs) in a cross-sectional survey of 13 small alpine communities in Tyrol (Austria). Data were collected retrospectively from self-administered questionnaires (n=796, 85% response), public records and lung function testing (n=752, 80% response). In the multivariate analysis it was found that a low birth weight (LBW), a low length of maternal education, a smaller gestational age, and a larger family size were all negatively associated with most lung function measures. Additionally, three significant interactions (birth weight with maternal education, birth weight with gestational age; and birth weight with family size) were observed. This implies that children of an LBW with mothers having a low level of education have a forced expiratory volume in one second (FEV1) value 148 mL lower than average values. Children born at term with an LBW have a 140 mL lower mean FEV1 value, and children of LBW from larger families display a 123 mL lower mean estimate of FEV1. However, subgroups were small (n=26, 17 and 27, respectively). The results support low birth weight as a significant predictor of decreased lung function at school age. However, the size and the direction of the association may differ depending on the levels of the interacting variables.

Intracoronary Stent Used in a Transplanted Heart.

The development of occlusive cardiac allograft vasculopathy is different from coronary artery disease in native vessels and treatment is still an unsettled problem. We describe a case of a 53-year-old male who underwent heart transplantation because of severe dilated cardiomyopathy. Based on myocardial ischemia, coronary angiography was performed six years later. Significant two-vessel coronary artery disease had developed and was treated by coronary angioplasty. Due to a suboptimal result, a Palmaz-Schatz stent was successfully implanted in the left anterior descending artery. The patency of the stent was demonstrated by ultrafast computed tomography and confirmed by control angiography three months later.