Inger Hagerman

Chaos-related deterministic regulation of heart rate variability in time- and frequency domains: effects of autonomic blockade and exercise

OBJECTIVES To study non-linear complexity or chaotic behaviour of heart rate in short time series and its dependence on autonomic tone. METHODS Ten healthy individuals (5 men, mean age 44 years) were investigated at rest, after intravenous injections of propranolol (0.15 mg/kg), followed by atropine (0.03 mg/kg). On another occasion, investigation was made during exercise on a bicycle ergometer at 40% and at 70% of maximal working capacity. Heart rate variability was assessed by: local sensitive dependence on initial conditions as quantitated by the dominant Lyapunov exponent, coefficient of variation of heart rate, power spectral analysis of high- and low-frequency bands and the 1/f-slope of the very-low-frequency band and time domain analysis. RESULTS The approximate dominant Lyapunov exponent was positive at rest and remained positive during autonomic blockade and during exercise. The exponent decreased significantly with propranolol+atropine and even more so during exercise but did not attain zero. At baseline approximate predictability was lost after about 30 s whereas after autonomic blockade or exercise it was lost after about 60 s. The 1/f-slope remained unaltered around -1. As expected, power in high- and low-frequency bands as well as time domain index decreased significantly with autonomic blockade. The low-frequency band and time domain index were affected by exercise. CONCLUSIONS Heart rate variability of sinus rhythm in healthy individuals has characteristics suggestive of low-dimensional chaos-like determinism which is modulated but not eliminated by inhibition of autonomic tone or by exercise. The dominant Lyapunov exponent characterises heart rate variability independent or the other investigated measures.

Parenteral Estrogen versus Combined Androgen Deprivation in the Treatment of Metastatic Prostatic Cancer - Scandinavian Prostatic Cancer Group (SPCG) Study No. 5

Objective : In the mid-1980s, interest in parenteral estrogen therapy for prostate cancer was renewed when it was found that it influenced liver metabolism only marginally and had very few cardiovascular side-effects. In this study high-dose polyestradiol phosphate (PEP; Estradurin ® ) was compared to combined androgen deprivation (CAD) for the treatment of patients with metastatic prostate cancer. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular side-effects. Material and Methods : A total of 917 patients with T0-4, NX, M1, G1-3 prostate cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter once a month or flutamide (Eulexin ® ) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl ® ) 3.75 mg per month i.m. or, on an optional basis, bilateral orchidectomy. A total of 556 patients had died at the time of this analysis. Results : There was no difference between the treatment arms in terms of time to biochemical or clinical progression and overall or disease-specific survival. There was no increase in cardiovascular mortality in the PEP arm. The PEP group had a higher prevalence of cardiovascular disease prior to the study and a significantly higher incidence of non-fatal ischemic heart events and heart decompensation during the study. Conclusions : PEP has an equal anticancer efficacy to CAD and does not increase cardiovascular mortality. Final evaluation of cardiovascular morbidity is awaiting further analysis and follow-up. PEP is considerably cheaper than CAD.

Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: Part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5

Objective. To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin®) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. Material and methods. In total, 910 eligible patients with T0–4, NX, M1, G1–3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0–2 were randomized to treatment with either PEP 240mg i.m. twice a month for 2months and thereafter monthly, or flutamide (Eulexin®) 250mg t.i.d. per os in combination with either triptorelin (Decapeptyl®) 3.75mg i.m. per month or on an optional basis bilateral orchidectomy. Results. At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). Conclusions. PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.

Weight monitoring in patients with severe heart failure (WISH). A randomized controlled trial.

This multicentre, randomized controlled trial hypothesized that daily electronic transmission of body weight to a heart failure (HF) clinic will reduce cardiac hospitalization in patients recently hospitalized with HF.

Three decades of heart transplantation in Scandinavia: long-term follow-up

Heart transplantation (HTx) has become a standard treatment for patients with end‐stage heart disease. The aim of this study was to report the long‐term outcome after HTx in Scandinavia.

Long-term follow-up of lung and heart transplant recipients with pre-transplant malignancies

BACKGROUND Concern regarding recurrence of pre-transplant (Tx) malignancy has disqualified patients from Tx. Because this has been poorly studied in lung and heart Tx recipients our aim was to investigate the influence of pre-Tx malignancy on post-Tx recurrence and long-term survival, focusing on pre-operative cancer-free intervals. METHODS From our lung and heart Tx programs (1983 to 2011) we retrospectively identified 111 (lung, 37; heart, 74) of 3,830 recipients with 113 pre-Tx malignancies. The patients were divided into 3 groups by pre-Tx cancer-free interval: Group I, <12 months (n = 24); Group II, ≥12 to<60 months (n = 18); and Group III, ≥60 months (n = 71). RESULTS Mean age at pre-Tx malignancy was 35±18 years. Mean post-Tx follow-up time was 70±63 months (range, 0-278 months), and malignancy recurrence was 63% in Group I, 26% in Group II, and 6% in Group III. Kaplan-Meier analysis of freedom from post-Tx recurrence revealed the following differences among the groups: Group I vs II, p = 0.08; II vs III, p = 0.002; and I vs III, p<0.001. Overall survival (51 deaths) was significantly poorer in Group I than in Groups II and III (p = 0.044). Survival between Groups II and III did not differ significantly (p = 0.93). CONCLUSIONS Cancer-free survival of ≥5 years pre-Tx is associated with the lowest recurrence. However, recurrence is related to the time the patients were cancer-free, as seen in Groups I and II.

Extracorporeal membrane oxygenation as a rescue of intractable ventricular fibrillation and bridge to heart transplantation.

Extracorporeal membrane oxygenation (ECMO) systems have undergone rapid technological improvements and are now feasible options for medium‐term support of severe cardiac or pulmonary failure. Intractable ventricular arrhythmia is a rare but well‐established indication for heart transplantation. We report a case of persistent ventricular fibrillation (VF) that was rescued by insertion of peripheral veno‐arterial ECMO during cardiopulmonary resuscitation, which provided support for 30 h of continuous VF and subsequently permitted urgent heart transplantation.

A Novel System for Source Characterization and Controlled Human Exposure to Nanoparticle Aggregates Generated During Gas–Metal Arc Welding

The aim of this study was to achieve a method to perform detailed characterization and human exposure studies of nanosized and nanostructured aerosol particles. The source chosen was mild steel, active gas, arc welding fume. The setup consisted of a generation chamber, where welding can be performed, connected to an airtight stainless steel 22 m3 exposure chamber. Instrumentation, consisting of a tapered element oscillating microbalance, a scanning mobility particle sizer, and a sampler for electron microscopy and particle-induced X-ray emission analysis was connected to the stainless steel chamber. The feasibility of the system for human exposure studies was evaluated by exposing 31 human volunteers, in groups of three, to a test aerosol containing 1 mg/m3 welding fumes and to conditioned, filtered air. The results show that an aerosol that accurately represents dilute welding fume exposures that occur in workplaces can be produced in a controlled manner, and that the experimental setup can be used for 6 h, double-blind, exposures of human subjects. Particle mass concentration levels could be varied from <5 μg/m3 to more than 1000 μg/m3. Fumes from metal active gas welding showed a unimodal size distribution with a mean mobility diameter of 160 nm, transmission electron microscopy showed aggregates with a clearly nanosized structure. Copyright 2013 American Association for Aerosol Research

Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer : Evaluation of cardiovascular events in a randomized trial

Abstract Objective. This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease. Material and methods. Nine-hundred and fifteen patients with T0–4, Nx, M1, G1–3, hormone- naïve prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression. Results. There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p < 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036). Conclusions. Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e.g. avoidance of osteopenia and hot flushes and the low price, are given priority.

Prevalence and prognostic impact of kidney disease on heart failure patients

Objectives The aim was to determine the prevalence of different degrees of kidney dysfunction and to examine their association with short-term and long-term outcomes in a large unselected contemporary heart failure population and some of its subgroups. We examined to what extent the different cardiac conditions and their severity contribute to the prognostic value of kidney dysfunction in heart failure. Design We studied 47 716 patients in the Swedish Heart Failure Registry. Patients were divided into five renal function strata based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. The adjusted association between kidney function and outcome was examined by Cox regression. Results 51% of the patients had eGFR <60 mL/min/1.73 m2 and 11% had eGFR <30. There was increasing mortality with decreasing kidney function regardless of age, presence of diabetes, New York Heart Association NYHA class, duration of heart failure and haemoglobin levels. The risk HR (95% CI) persisted after adjusting for differences in baseline characteristics, severity of heart disease, and medical treatment: eGFR 60–89: 0.86 (0.79 to 0.95); eGFR 30–59: 1.13 (1.03 to 1.24); eGFR 15–29: 1.85 (1.67 to 2.07); and eGFR <15: 2.96 ([2.53 to –3.47)], compared with eGFR ≥90. Conclusions Kidney dysfunction is common and strongly associated with short-term and long-term outcomes in patients with heart failure. This strong association was evident in all age groups, regardless of NYHA class, duration of heart failure, haemoglobin level, and presence/absence of diabetes mellitus. After adjusting for differences in baseline data, aetiology and severity of heart disease and treatment, the strong association remained.