Abstract Background Pocket haematomas are one of the most common complications post cardiovascular implantable electronic device (CIED) implantation. Objective We explored the use of mechanical compression devices compared to the conventional dressings post CIED implantation, to reduce the incidence of pocket haematomas. Secondary outcomes were pain scores and wound scar or healing. Methods Five electronic databases were systematically searched from their inception to 1st November 2023, identifying all studies which explored compression dressings post CIED implantation. Data were independently extracted by investigators according to predefined clinical endpoints. We used a Random-effects model for data analysis based on event rates (ER) and 95% confidence interval (CI). Results Six studies (786 patients) were included in the meta-analysis, with 373 in the compression arm and 385 patients in the control groups across the studies. There was a total incidence of 82 haematomas, of which 24.4% were in the mechanical compression group and 75.6% in the conventional dressings group (RR 0.36, 95% CI 0.23- 0.57). One study suggested improved wound healing with the compression dressing arm (Manchester Scar Scale 9.5 at 2 weeks for the control group and 7.5 for the compression dressings group). Two studies suggested increased pain scores (using a visual analogue scale) shortly after dressing application. One study suggested improved comfort scores in the compression group compared to the control at 48 hours and 7 days. Conclusion This systematic review and meta-analysis suggests for patients post CIED implantation, the use of novel mechanical compression dressings, when compared to conventional dressings, reduces the risk of pocket haematoma.Forest plot

Atrial fibrillation (AF) is the most common atrial arrhythmia leading to increased risk of thromboembolic events. It is often asymptomatic and paroxysmal in nature, making it difficult to detect using ward telemetry (WT) post cerebrovascular accident (CVA) leading to under utilisation of anticoagulation. This study compares conventional 2-day WT versus 4-day wireless S-patch monitoring to detect AF. This first in Australia dual-centre study was a prospective comparison pilot of the S-Patch monitor against WT monitors in 51 patients admitted for stroke workup. The patients were fitted with both WT monitoring for 2 days versus S-patch monitoring for 4 days in the detection of AF. 76 hours of telemetry were assessed via data extractions and Cardiologist review. A matrix was used to measure nursing/patient satisfaction and setup/resource times were assessed. 84–94% of patients and 75–95% of nursing preferred the S-Patch. Non-parametric tests indicate significant time saving for removal of S-Patch versus WT [2.2 mins vs 5.1 mins (p = 0.00)]. Efficacy of S-Patch to detect AF following Cardiologist review was greater than WT, with 7 patients identified with AF by S-Patch versus 1 using WT. The S-patch had a false positive rate of 78%. The S-patch had a higher detection rate of AF compared to WT. This allows patients to be anticoagulated appropriately for the prevention of future stroke. Patients and staff overwhelmingly prefer the S-Patch. The S-Patch is sensitive in the detection of AF, however it showed a high false positive rate where further refinement of the device would be beneficial.

We investigated the effects of three components of ischemia: external acidosis (pH=6.0), extracellular hyperkalemia ([K+]=20 mmol/l), and resting membrane depolarization to −60 mV, on Kv4.3 current stably expressed in Chinese Hamster Ovary cells. We used single electrode whole cell patch clamp techniques to study changes in the current elicited. External acidosis caused a positive shift in the steady state activation curve from −13.4±2.1 mV to −3.3±1.5 mV (n=8, P=0.004) and the steady state inactivation curve from −56.5±0.4 mV to −46.7±0.5 mV (n=14, P<0.0001). Acidosis also caused an acceleration of recovery from inactivation with the t1/2 decreasing from 306 ms (95% CI 287–327 ms) to 194 ms (95% CI 182–207 ms), (n=14, P<0.05). Hyperkalemia did not affect any of these parameters. Combined acidosis and hyperkalemia produced effects similar to those seen with acidosis. Changing the holding potential from −90 mV to −60 mV with test potentials of +5 and +85 mV decreased the peak currents by 34.1% and 32.4% respectively (n=14). However, in the presence of external acidosis the decrease in peak currents induced by changing the holding potential was less marked. In acidotic bath the peak current at −60 mV was reduced by only 13.6% at a test potential of +5 mV and 12.3% at a test potential of +85 mV (n=14). Taken together our data suggest that the membrane depolarization and changes in pH which occur under ischemic conditions would be accompanied by relative preservation of Kv4.3 currents and provide a molecular basis for the observation of preserved epicardial Ito and epicardial action potential duration (APD) shortening in ischemia.

Tie, Hui MBBS; Walker, Bruce D. MBBS; Singleton, Cameron B. MBBS; Bursill, Jane A. BTC; Wyse, Ken R. BSc; Campbell, Terry J. MD, DPhil; Valenzuela, Stella M. PhD; Breit, Samuel N. MD Author Information

Objective: To evaluate the effects of azimilide and ambasilide on the biophysical properties of the human-ether-a-go-go-related (HERC) channel. Methods: HERG was stably transfected into Chinese hamster ovary (CHO-K1) cells and currents were measured using a whole cell, voltage-clamp technique. Results: Azimilide had a 'dual effect', inhibiting current at voltage steps above -40 mV and augmenting current at -40 and -50 mV. Tail current inhibition following a step to +30 mV did not vary with temperature (IC50 610 nM at 22 degrees C and 560 nM at 37 degrees C). The agonist effect at -50 mV was concentration-dependent and correlated with a hyperpolarizing shift in the V-1/2 of activation (r = 0.98, P < 0.05). Time constants of inactivation were faster and there was a -10 mV shift in the V-1/2 of steady state inactivation suggestive of open and inactivated state binding. By comparison, ambasilide inhibited HERG channels with lower potency (IC50 3.6 mu M), in a voltage- and time-dependent but frequency-independent manner (0.03-1 Hz). Ambasilide had no effect on activation or inactivation gating but prolonged both fast and slow components of deactivation consistent with unbinding from the open state. The net effect of both drugs was similar during a voltage ramp which simulated a cardiac action potential. Conclusions: Inhibition of HERG channels by azimilide and ambasilide exhibits a similar time and voltage-dependence. While both exhibit affinity for the open state, azimilide also binds to inactivated channels. (C) 2000 Elsevier Science B.V. All rights reserved.

Halofantrine is a widely used antimalarial agent which has been associated with prolongation of the 'QT interval' of the electrocardiogram (ECG), torsades de pointes and sudden death. Whilst QT prolongation is consistent with halofantrine-induced increases in cardiac ventricular action potential duration, the cellular mechanism for these observations has not been previously reported. The delayed rectifier potassium channel, I(Kr), is a primary site of action of drugs causing QT prolongation and is encoded by the human-ether-a-go-go-related gene (HERG). We examined the effects of halofantrine on HERG potassium channels stably expressed in Chinese hamster ovary (CHO-K1) cells. Halofantrine blocked HERG tail currents elicited on repolarization to -60 mV from +30 mV with an IC(50) of 196.9 nM. The therapeutic plasma concentration range for halofantrine is 1.67-2.98 microM. Channel inhibition by halofantrine exhibited time-, voltage- and use-dependence. Halofantrine did not alter the time course of channel activation or deactivation, but inactivation was accelerated and there was a 20 mV hyperpolarizing shift in the mid-activation potential of steady-state inactivation. Block was enhanced by pulses that render channels inactivated, and channel blockade increased with increasing duration of depolarizing pulses. We conclude that HERG channel inhibition by halofantrine is the likely underlying cellular mechanism for QT prolongation. Our data suggest preferential binding of halofantrine to the open and inactivated channel states.

1. The Kv4.3 gene is believed to encode a large proportion of the transient outward current (Ito), responsible for the early phase of repolarization of the human cardiac action potential. There is evidence that this current is involved in the dispersion of refractoriness which develops during myocardial ischaemia and which predisposes to the development of potentially fatal ventricular tachyarrhythmias. 2. Epidemiological, clinical, animal, and cellular studies indicate that these arrhythmias may be ameliorated in myocardial ischaemia by n-3 polyunsaturated fatty acids (n-3 PUFA) present in fish oils. 3. We describe stable transfection of the Kv4.3 gene into a mammalian cell line (Chinese hamster ovary cells), and using patch clamp techniques have shown that the resulting current closely resembles human Ito. 4. The current is rapidly activating and inactivating, with both processes being well fit by double exponential functions (time constants of 3.8 +/- 0.2 and 5.3 +/- 0.4 ms for activation and 20.0 +/- 1.2 and 96.6+/-6.7 ms for inactivation at +45 mV at 23 degrees C). Activation and steady state inactivation both show voltage dependence (V1/2 of activation= -6.7+/-2.5 mV, V1,2 of steady state inactivation= -51.3+/-0.2 mV at 23 degrees C). Current inactivation and recovery from inactivation are faster at physiologic temperature (37 degrees C) compared to room temperature (23 degrees C). 5. The n-3 PUFA docosahexaenoic acid blocks the Kv4.3 current with an IC50 of 3.6 micromol L(-1). Blockade of the transient outward current may be an important mechanism by which n-3 PUFA provide protection against the development of ventricular fibrillation during myocardial ischaemia.

Perhexiline has been used as an anti‐anginal agent for over 25 years, and is known to cause QT prolongation and torsades de pointes. We hypothesized that the cellular basis for these effects was blockade of IKr. A stable transfection of HERG into a CHO‐K1 cell line produced a delayed rectifier, potassium channel with similar properties to those reported for transient expression in Xenopus oocytes. Perhexiline caused voltage‐ and frequency‐dependent block of HERG (IC50 7.8 μM). The rate of inactivation was increased and there was a 10 mV hyperpolarizing shift in the voltage‐dependence of steady‐state inactivation, suggestive of binding to the inactivated state. In conclusion, perhexiline potently inhibits transfected HERG channels and this is the probable mechanism for QT prolongation and torsades de pointes. Channel blockade shows greatest affinity for the inactivated state. British Journal of Pharmacology (1999) 127, 243–251; doi:10.1038/sj.bjp.0702502