Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure

© 2017, Springer-Verlag Berlin Heidelberg. Aims: Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents. Methods and results: 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71–0.91, p  <  0.01, and HR 0.86, 95% CI 0.78–0.94, p  <  0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82–1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76–1.06; p = 0.20; HR 1.10, 95% CI 0.93–1.31, p = 0.24; and HR 1.08, 95% CI 0.95–1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups. Conclusion: Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF

Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation

Background: In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods: We performed a post hoc analysis of the BIOSTAT-CHF study. We evaluated 1548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure hospitalisation stratified by heart rhythm and heart rate at baseline. Results: Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at 9 months was associated with reduced incidence of the primary outcome in both SR and AF patients [HR per 10 bpm decrease—SR: 0.83 (0.75–0.91), p &lt; 0.001; AF: 0.89 (0.81–0.98), p = 0.018], whereas the relationship was less strong for achieved heart rate in AF [HR per 10 bpm higher—SR: 1.26 (1.10–1.46), p = 0.001; AF: 1.08 (0.94–1.23), p = 0.18]. Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions: Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate

Overview of diagnosis and management of paediatric headache. Part I: diagnosis

Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life

Thoracic Epidural Catheter Placement Using a Paramedian Approach with Cephalad Angulation in Three Dogs

Objective To describe a technique for insertion of a thoracic epidural catheter. Study Design Clinical report. Animals Dogs (n = 3) undergoing thoracic wall resection and thoracotomy. Methods A paramedian approach with cephalic angulation was used to place a 24-g epidural catheter in 3 dogs. Dogs 1 and 2 had left caudal thoracic wall resection and dog 3 had left thoracotomy. In dog 1, the epidural catheter was inserted at L2\u2013L3 intervertebral space and the tip of the catheter advanced to the level of T13 vertebral body. In dog 2, the epidural catheter was inserted at T12\u2013T13 intervertebral space and the tip of the catheter was advanced to the level of T8 vertebral body. In dog 3, the epidural catheter was inserted at T13\u2013L1 intervertebral space and its tip advanced until reaching the vertebral body of T10. All dogs were administered a combination of bupivacaine and morphine through the epidural catheter to provide intra- and postoperative analgesia. Results The peridural space was identified and the tip of the catheter was positioned where intended in all dogs. Dog 1 developed transient Horner's syndrome and dog 3 required intraoperative fentanyl during the first part of the procedure. Conclusion Paramedian approach with cephalad angulation is a suitable technique to place thoracic epidural catheters in dogs

Ultrasound-guided parasternal injection in dogs: a cadaver study

Objectives: To describe the technique of performing an ultrasound-guided distal parasternal intercostal block and to determine the distribution of two volumes of methylene blue dye solution injected in canine cadavers. Study design: Prospective cadaver study. Animals: A group of seven canine cadavers weighing 12–34 kg. Methods: The space between the transversus thoracic and the internal intercostal muscles is a virtual cavity. Ultrasound-guided injections in the distal (parasternal) intercostal space were performed using dye solution at 0.05 mL kg–1 in each intercostal space from the second to seventh (LV, low volume, six injections per dog) in one hemithorax, and 0.1 mL kg–1 in the third, fifth and seventh intercostal spaces (HV, high volume, three injections in each dog) on the contralateral side. Anatomical dissection was carried out to describe dye spread characteristics and staining of intercostal nerves. Results: The ultrasonographic landmarks for injection were identified in each cadaver. In the LV group the solution was found in every intercostal space (36/36), whereas the HV injection stained six intercostal spaces in two dogs, five in two, and in two dogs the solution was found in four and three spaces, respectively, demonstrating multisegmental distribution. Intrapleural staining was observed after two injections. Conclusions and clinical relevance: Ultrasound-guided injection of 0.05 mL kg–1 at the distal intercostal space resulted in staining of the intercostal nerve in all dogs when performed in every space and may be an appropriate alternative to previously reported techniques. A single injection of 0.1 mL kg–1 may anaesthetize more than one intercostal nerve, but not consistently. Clinical investigations are warranted to better characterize and to refine this locoregional technique