Device updates successfully reduce T­wave oversensing and inappropriate shocks in subcutaneous ICD patients.

AIMS: To analyse the impact of device and software updates on the prevention of T­wave oversensing (TWOS) and inappropriate shocks (IS) in subcutaneous ICD (S-ICD) patients. BACKGROUND: TWOS is a feared complication after implantation. It may lead to harmful IS. To date, specific strategies to reduce these events are lacking. METHODS: In this retrospective single-centre trial we analysed 146 S­ICD patients who were implanted between 2010 and 2016. In all eligible consecutive patients (n = 139), follow-up of at least 6 weeks was studied. The incidence of TWOS/IS was analysed in patients receiving a 2nd generation S­ICD (Emblem-S-ICD) between 2014 and 2016 (Emblem). Their outcome was compared with a control group (SQ) treated with the SQ1010 device between 2010 and 2014, who were followed up for a maximum of 2 years. Furthermore, to test if the software update SMR8 reduces inappropriate shocks in the SQ1010-S-ICD population, the incidence of TWOS/IS was evaluated before and after update installation. RESULTS: Basic characteristics and indications for S­ICD implantation were similar in both groups. However, the cumulative incidence of TWOS/IS was significantly decreased in Emblem vs. SQ (SQ: 15.4%, n = 14/91 vs. Emblem 4.2%, n = 2/48; p = 0.049). Furthermore, with regards to the SQ population we also observed a trend towards a significant reduction of TWOS/IS after installation of the software update SMR8 in 2014 (before update: 13.4%, n = 11/82 vs. after update: 4.6%, 3/65, p = 0.07). CONCLUSION: 2nd generation devices but probably also the SMR8 software update reduce the incidence of TWOS/IS in S­ICD patients.

Long-QT syndrome-associated caveolin-3 mutations differentially regulate the hyperpolarization-activated cyclic nucleotide gated channel 4.

Background Caveolin-3 (cav-3) mutations are linked to the long-QT syndrome (LQTS) causing distinct clinical symptoms. Hyperpolarization-activated cyclic nucleotide channel 4 (HCN4) underlies the pacemaker current If. It associates with cav-3 and both form a macromolecular complex. Methods To examine the effects of human LQTS-associated cav-3 mutations on HCN4-channel function, HEK293-cells were cotransfected with HCN4 and wild-type (WT) cav-3 or a LQTS-associated cav-3 mutant (T78M, A85T, S141R, or F97C). HCN4 currents were recorded using the whole-cell patch-clamp technique. Results WT cav-3 significantly decreased HCN4 current density and shifted midpoint of activation into negative direction. HCN4 current properties were differentially modulated by LQTS-associated cav-3 mutations. When compared with WT cav-3, A85T, F97C, and T78M did not alter the specific effect of cav-3, but S141R significantly increased HCN4 current density. Compared with WT cav-3, no significant modifications of voltage dependence of steady-state activation curves were observed. However, while WT cav-3 alone had no significant effect on HCN4 current activation, all LQTS-associated cav-3 mutations significantly accelerated HCN4 activation kinetics. Conclusions Our results indicate that HCN4 channel function is modulated by cav-3. LQTS-associated mutations of cav-3 differentially influence pacemaker current properties indicating a pathophysiological role in clinical manifestations.

Influence of low-molecular-weight heparin dosage on red blood cell transfusion, lymphocele rate and drainage duration after open radical prostatectomy.

BACKGROUND: To assess the rates of red blood cell (RBC) transfusions, pelvic lymphoceles, and prolonged drainage duration in patients after radical prostatectomy (RP) receiving perioperative bridging with low-molecular-weight heparin (LMWH). PATIENTS AND METHODS: Between 2006 and 2009, 114 RP patients receiving bridging therapy with 60 mg (n = 63) or ≥80 mg (n = 51) Enoxaparin/d were compared to 1327 consecutive RP patients receiving 40 mg Enoxaparin/d. Logistic regression models were used to test the effect of LMWH dosage on all three outcomes. Covariables included age, body mass index (BMI), Charlson comorbidity index (CCI), prostate volume, pelvic lymph node dissection, and pathological stage. RESULTS: The RBC transfusion rates in patients treated with 40, 60 and ≥80 mg were 4.9, 9.5 and 19.6%, respectively (p < 0.001). The respective lymphocele rates were 6.4, 3.2 and 2.0% (p = 0.26). The respective rates of drainage duration of ≥4 days were 6.7, 4.8 and 16.7% (p = 0.088). After adjusting for confounding factors, patients receiving ≥80 mg were 4.1-fold more likely to be transfused than patients receiving prophylactic LMWH (p = 0.02). Similarly, patients receiving ≥80 mg were 3.2-fold more likely to have a drainage duration of ≥4 days than patients receiving prophylactic LMWH (p = 0.03). CONCLUSIONS: Patients with a perioperative bridging with LMWH in RP are more likely to receive a RBC transfusion and to have prolonged drainage duration. Conversely, bridging therapy was not associated with an increased risk of lymphocele formation.