Effects of structured heart failure disease management on mortality and morbidity depend on patients' mood: results from the Interdisciplinary Network for Heart Failure Study.

AIMS: Depression is common in heart failure (HF) and associated with adverse outcomes. Randomized comparisons of the effectiveness of HF care strategies by patients' mood are scarce. We therefore investigated in a randomized trial a structured collaborative disease management programme (HeartNetCare-HF™; HNC) recording mortality, morbidity, and symptoms in patients enrolled after hospitalization for decompensated systolic HF according to their responses to the 9-item Patient Health Questionnaire (PHQ-9) during an observation period of 180 days. METHODS AND RESULTS: Subjects scoring <12/≥12 were categorized as non-depressed/depressed, and those ignoring the questionnaire as PHQ-deniers. Amongst 715 participants (69 ± 12 years, 29% female), 141 (20%) were depressed, 466 (65%) non-depressed, and 108 (15%) PHQ-deniers. The composite endpoint of mortality and re-hospitalization was neutral overall and in all subgroups. However, HNC reduced mortality risk in both depressed and non-depressed patients [adjusted hazard ratios (HRs) 0.12, 95% confidence interval (CI) 0.03-0.56, P = 0.006, and 0.49, 95% CI 0.25-0.93, P = 0.03, respectively], but not in PHQ-deniers (HR 1.74, 95% CI 0.77-3.96, P = 0.19; P = 0.006 for homogeneity of HRs). Average frequencies of patient contacts in the HNC arm were 12.8 ± 7.9 in non-depressed patients, 12.4 ± 7.1 in depressed patients, and 5.5 ± 7.2 in PHQ-deniers (P < 0.001). CONCLUSIONS: Early after decompensation, HNC reduced mortality risk in non-depressed and even more in depressed subjects, but not in PHQ-deniers. This suggests that differential acceptability and chance of success of care strategies such as HNC might be predicted by appropriate assessment of patients' baseline characteristics including psychological disposition. These post-hoc results should be reassessed by prospective evaluation of HNC in larger HF populations.

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice.

Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention.

Continuous wound infiltration with ropivacaine reduces pain and analgesic requirement after shoulder surgery.

UNLABELLED: After achieving a reduction of pain scores for 10 h with a single dose wound infiltration after shoulder surgery, we examined in a prospective, placebo-controlled and double-blinded study the analgesic effects of continuous wound infiltration with different concentrations of ropivacaine. Forty-five patients undergoing shoulder surgery were randomly assigned into three groups to receive single dose wound infiltration with 30 mL saline (group S) or ropivacaine 7.5 mg/mL (groups R2 and R3.75) after skin closure. Postoperatively, patients received a continuous wound infiltration with saline (group S), ropivacaine 2 mg/mL (group R2) or ropivacaine 3.75 mg/mL (group R3.75) for 48 h. Supplemental pain relief was provided by IV patient-controlled analgesia with the opioid piritramide. At 1, 2, 3, 4, 24, and 48 h postoperatively visual analogue scale (VAS) values (0-100 mm), piritramide requirements and side effects were registered. Plasma levels of ropivacaine were measured preoperatively and at 24 h and 48 h after surgery. Until 48 h VAS values were smaller in group R3.75 compared with group S (group R3.75, 8 +/- 9 mm; group S, 31 +/- 14 mm; P < 0.005), whereas 4 h and 48 h postoperatively VAS values were even smaller in group R3.75 compared with group R2 (P < 0.05). Cumulative piritramide consumption was always smaller in groups R2 and R3.75 compared with group S (1-24 h, P < 0.005; 48 h, P < 0.05). Plasma ropivacaine levels remained less than the toxic threshold. We conclude that continuous postoperative wound infiltration with ropivacaine, especially using 3.75 mg/mL, provides smaller VAS values and opioid requirement in comparison with saline after shoulder surgery. IMPLICATIONS: The continuous postoperative wound infiltration after shoulder surgery with different concentrations of ropivacaine, 2 mg/mL and 3.75 mg/mL, results in lower pain scores and opioid requirement compared with infiltration with placebo. Plasma levels of ropivacaine remained less than the toxic threshold.